Mometasone Furoate/formoterol Research Articles

P450 CLINICAL MEASURES OF ASTHMA CONTROL FROM THE MOMETASONE FUROATE/FORMOTEROL SPIRO TRIAL

Asthma maintenance treatment aims to preserve asthma control in order to reduce the risk of asthma exacerbation. The combination between an inhaled corticosteroid and a fast-acting bronchodilator, systemic corticosteroids (SCS) bursts and other add-on asthma medications are prescribed for asthma worsening to mitigate serious outcomes.1 Primary findings from a 26-week double-blind, randomized-controlled trial in patients ≥12 years of age with persistent asthma comparing mometasone furoate/formoterol (MF/F) to MF did not demonstrate a significant difference in asthma-related hospitalizations, intubations and deaths, but did show a significant reduction in asthma exacerbation.2 The present analysis of additional prespecified endpoints further characterizes MF/F effects on clinical measures of asthma control.

P211 EFFICACY AND SAFETY OF MOMETASONE FUROATE/FORMOTEROL COMPARED WITH MOMETASONE FUROATE IN CHILDREN WITH PERSISTENT ASTHMA

Asthma affects over 6 million children in the United States alone. This study investigated the efficacy and long-term safety of mometasone furoate-formoterol (MF/F) and MF monotherapy in children with persistent asthma.

Serious asthma events with mometasone furoate plus formoterol compared with mometasone furoate

The safety of long-acting β-agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial. We sought to determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes (SAOs) compared with mometasone furoate alone. This clinical trial is registered as NCT01471340. We conducted a 26-week, randomized, double-blind trial in adolescent and adult patients (≥12years) with persistent asthma in 35 countries with the primary objective of evaluating whether mometasone furoate-formoterol increases the risk of SAOs (adjudicated hospitalization, intubation, or death) compared with mometasone furoate alone. The key efficacy end point was asthma exacerbation (composite of hospitalization of ≥24hours, emergency department visits of <24hours requiring systemic corticosteroids, or use of systemic corticosteroids for ≥3 consecutive days). Among 11,729 patients (mometasone furoate-formoterol, n=5,868; mometasone furoate, n=5,861), a total of 81 SAOs, all asthma-related hospitalizations, were observed in 71 patients: 45 events from 39 patients receiving mometasone furoate-formoterol and 36 events from 32 patients receiving mometasone furoate. The hazard ratio for the first SAO in the mometasone furoate-formoterol versus mometasone furoate group was 1.22 (95% CI, 0.76-1.94; P=.411). Asthma exacerbation occurred in 1,487 patients: 708 receiving mometasone furoate-formoterol and 779 receiving mometasone furoate. The hazard ratio for the first asthma exacerbation in the mometasone furoate-formoterol versus mometasone furoate group was 0.89 (95% CI, 0.80-0.98; P=.021). The addition of formoterol to mometasone furoate maintenance therapy did not increase the risk of serious asthma-related events and reduced the risk of asthma exacerbation.

New fixed dose combination in treatment of asthma: focus on mometasone furoate/formoterol

The review focused on mometasone furoate/formoterol (MF/F), a new fixed dose combination (Zenhale, MDI 50/5, 100/5 and 200/5 mcg/dose) for treatment of asthma in adults and children 12 years of age and older. New combination should be used for patients not adequately controlled with inhaled corticosteroids (ICS) and «as needed» inhaled short acting β 2-agonist or those whose disease severity warrants initiation of treatment with two maintenance therapies. It may be also used in patients already adequately controlled on both ICS and long-acting β 2-agonist. Data from randomized placebo controlled clinical trials confirm that MF/F has fast onset of action, reduces number of exacerbations, improves lung function, quality of life and asthma control. MF/F has a good safety profile.

Hypothalamic-Pituitary-Adrenal Axis Effects of Mometasone Furoate/Formoterol Fumarate vs Fluticasone Propionate/Salmeterol Administered Through Metered-Dose Inhaler

The effects of mometasone furoate and fluticasone propionate on the hypothalamic-pituitary-adrenal axis were compared when administered from combination metered-dose inhaler (MDI) products. In a randomized, open-label, placebo-controlled, parallel group study, 66 patients with mild to moderate asthma received one of the following four treatments bid through an MDI for 42 days: mometasone furoate/formoterol (MF/F) 200 μg/10 μg, MF/F 400 μg/10 μg, fluticasone propionate/salmeterol (FP/S) 460 μg/42 μg, or placebo. Plasma cortisol concentrations were measured over 24 h on days -1 (baseline) and 42. Geometric mean ratio (GMR) and 90% CI for mean change from baseline to day 42 in 24-h plasma cortisol area under the curve (AUC) were calculated for each treatment. If the 90% CI for the GMRs fell within 70% to 143%, treatments were deemed comparable. Mean baseline cortisol AUCs were similar across groups. Mean cortisol effects (change from baseline) were similar for MF/F 400 μg/10 μg and FP/S 460 μg/42 μg (GMR, 119%; 90% CI, 101%-140%). Effects of MF/F 200 μg/10 μg on cortisol AUC were similar to placebo (GMR, 92%; 90% CI, 78%-110%), whereas MF/F 400 μg/10 μg and FP/S 460 μg/42 μg lowered cortisol AUC vs placebo (GMR, 78% [90% CI, 66%-92%] and 66% [90% CI 56%-78%], respectively). All treatments were generally well tolerated. MF/F 400 μg/10 μg or FP/S 460 μg/42 μg bid through an MDI led to similar reductions from baseline in mean cortisol AUC (22% and 34% lower than placebo, respectively), whereas the effect of MF/F 200 μg/10 μg was similar to placebo.

Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease.

Both long-acting beta(2)-agonists and inhaled corticosteroids have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease (COPD). Their co-administration in a combined inhaler is intended to facilitate adherence to medication regimens and to improve efficacy. Three preparations are currently available: fluticasone propionate/salmeterol (FPS). budesonide/formoterol (BDF) and mometasone furoate/formoterol (MF/F). To assess the efficacy and safety of combined long-acting beta2-agonist and inhaled corticosteroid (LABA/ICS) preparations, as measured by clinical endpoints and pulmonary function testing, compared with inhaled corticosteroids (ICS) alone, in the treatment of adults with chronic obstructive pulmonary disease (COPD). We searched the Cochrane Airways Group Specialised Register of trials, which is compiled from systematic searches of multiple literature databases. The search was conducted in June 2013. In addition, we checked the reference lists of included studies and contacted the relevant manufacturers. Studies were included if they were randomised and double-blind. Compared studies combined LABA/ICS with the ICS component. Two review authors independently assessed trial quality and extracted data. The primary outcomes were exacerbations, mortality and pneumonia. Health-related quality of life (as measured by validated scales), lung function and side effects were secondary outcomes. Dichotomous data were analysed as fixed-effect odds ratios with 95% confidence intervals (CIs), and continuous data as mean differences or rate ratios and 95% CIs. A total of 15 studies of good methodological quality met the inclusion criteria by randomly assigning 7814 participants with predominantly poorly reversible, severe COPD. Data were most plentiful for the FPS combination. Exacerbation rates were significantly reduced with combination therapies (rate ratio 0.87, 95% CI 0.80 to 0.94, 6 studies, N = 5601) compared with ICS alone. The mean exacerbation rate in the control (ICS) arms of the six included studies was 1.21 exacerbations per participant per year (range 0.88 to 1.60), and we would expect this to be reduced to a rate of 1.05 (95% CI 0.97 to 1.14) among those given combination therapy. Mortality was also lower with the combination (odds ratio (OR) 0.78, 95% CI 0.64 to 0.94, 12 studies, N = 7518) than with ICS alone, but this was heavily weighted by a three-year study of FPS. When this study was removed, no significant mortality difference was noted. The reduction in exacerbations did not translate into significantly reduced rates of hospitalisation due to COPD exacerbation (OR 0.93, 95% CI 0.80 to 1.07, 10 studies, N = 7060). Lung function data favoured combination treatment in the FPS, BDF and MF/F trials, but the improvement was small. Small improvements in health-related quality of life were measured on the St George's Respiratory Questionnaire (SGRQ) with FPS or BDF compared with ICS, but this was well below the minimum clinically important difference. Adverse event profiles were similar between the two treatments arms, and rates of pneumonia when it was diagnosed by chest x-ray (CXR) were lower than those reported in earlier trials. Combination ICS and LABA offer some clinical benefits in COPD compared with ICS alone, especially for reduction in exacerbations. This review does not support the use of ICS alone when LABAs are available. Adverse events were not significantly different between treatments. Further long-term assessments using practical outcomes of current and new 24-hour LABAs will help determine their efficacy and safety. For robust comparisons as to their relative effects, long-term head-to-head comparisons are needed.

Dose-dependent anti-inflammatory effect of inhaled mometasone furoate/formoterol in subjects with asthma

A well-controlled study in patients with allergic asthma was warranted to assess dose-dependency between fractional concentration of exhaled nitric oxide (FeNO) and sputum eosinophils to a combination of an inhaled corticosteroid plus a long-acting β2-agonist. We sought to characterize the dose-dependency of mometasone furoate/formoterol (MF/F) using FeNO and sputum eosinophil percentage as surrogates of airway inflammation in subjects with allergic asthma. Following a 2-week, open-label run-in, 93 subjects (≥12y) using only short-acting beta agonist reliever medication as needed, were randomized to twice daily (BID) placebo; MF/F 100/10μg, 200/10μg, or 400/10μg (via pressurized metered-dose inhaler [MDI]); MF-MDI 200μg; or MF 200μg via dry powder inhaler (DPI) during a 2-week, double-blind treatment period. All active treatments demonstrated significant percentage reductions from baseline in FeNO compared with placebo at all time points (P≤0.034). At endpoint, mean MF/F treatment group FeNO reductions ranged from -35.3% to -61.4%. Sputum eosinophil percentage reductions from baseline were significant compared with placebo for the MF/F 200/10μg, MF/F 400/10μg, and MF-DPI 200μg groups at endpoint (P≤0.023). Escalating MF/F doses significantly reduced both FeNO (P≤0.001) and sputum eosinophil (P≤0.022) levels in a dose-dependent manner at all time points. All treatments were well tolerated; no serious adverse events were observed. All 3MF/F doses demonstrated pronounced, clinically meaningful, dose-dependent reductions in FeNO, with reduced sputum eosinophil levels for MF/F 200/10μg and MF/F 400/10μg. These findings suggest both inflammatory markers may be useful in assessing corticosteroid responsiveness in asthma patients, and perhaps identifying the same asthma subphenotype. Clinical Trials.gov: NCT00635882.

189 Efficacy and Safety of Two Doses of Mometasone Furoate/Formoterol Combination Treatment in Subjects With Severe Asthma

BackgroundMultiple strengths of mometasone furoate/formoterol (MF/F) metered-dose inhaler combination therapy have been investigated as new treatments for asthma. We report efficacy/safety findings from an MF/F study in subjects with severe asthma previously uncontrolled on high-dose inhaled corticosteroids (ICS) with or without a long-acting ß2-agonist (LABA).MethodsThis was a 3-month, randomized, double-blind, parallel-group, multicenter study with a 2- to 3-week open-label run-in period during which subjects received mometasone furoate (MF) 400 μg twice daily (BID). Subjects (≥12 years) were randomized to MF/F 200/10 μg BID, MF/F 400/10 μg BID, or MF 400 μg BID. The primary endpoint was the area under the curve (AUC) of the change in serial (0−12 hours) forced expiratory volume in 1 second (FEV1) for MF/F 400/10 μg vs MF 400 μg from baseline to week 12. Adverse events (AEs) and other clinical safety measures were recorded.Results728 subjects were randomized (mean: age, 47.9 years; asthma duration, 14.0 years; FEV1 % predicted, 66.3; reversibility, 22.9%; Asthma Control Questionnaire score, 1.93). Improvements in mean changes from baseline in FEV1 AUC0−12h at week 12 were: MF/F 200/10 μg = 3.59 L × h; MF/F 400/10 μg = 4.19 L × h; MF 400 μg = 2.04 L × h, with both MF/F doses significantly better than MF (P < 0.001). These FEV1 AUC0–12h values with MF/F 200/10 μg, MF/F 400/10 μg, and MF 400 μg correspond to average hourly increases of 0.30, 0.35, and 0.17 L, respectively. MF/F was associated with a rapid (<5 minutes) and sustained improvement in lung function. The percentages of subjects experiencing an asthma deterioration (ie, severe asthma exacerbation) were 12.4% (MF/F 200/10 μg), 12.2% (MF/F 400/10 μg), and 18.3% (MF 400 μg). There were no notable differences in AEs between the groups.ConclusionsBoth the 200/10 μg BID and 400/10 μg BID doses of MF/F combination therapy led to significantly greater improvements in lung function compared with 400 μg BID MF monotherapy in subjects with severe asthma previously treated with an ICS alone or in combination with LABA.

192 Efficacy and Safety of Combined Mometasone Furoate/Formoterol 100/10ìG Twice Daily in Subjects with Asthma Inadequately Controlled on Low-Dose Inhaled Corticosteroids

BackgroundAsthma is a variable disease. Optimal control in clinical practice often requires the use of therapy at varying doses. Availability of treatments at multiple strengths is therefore essential. These are results from a 6-month trial of combined mometasone furoate/formoterol (MF/F) 100/10 μg administered via a metered-dose inhaler (MDI) as treatment for asthma deterioration (ie, severe asthma exacerbation) and bronchoconstriction in asthmatics previously treated with low-dose inhaled corticosteroids (ICS).MethodsIn a randomized, multicenter, double-blind, placebo-controlled study in asthma subjects (≥12 years) on ICS with/without a long-acting β2-agonist (LABA), subjects were assigned to 2 to 3 weeks of open-label MF 100 twice daily (BID), followed by 26 weeks of MF/F 100/10 μg, MF 100 F 10 or placebo (all BID). Co-primary endpoints were time to first asthma deterioration across the 26-week treatment period (MF/F versus F) and change from baseline to week 12 in serial (0−12 hours) forced expiratory volume in 1 second (FEV1) (MF/F vs MF). Adverse events (AEs) were monitored.Results746 subjects (mean: age = 38.3 years, asthma duration = 14.77 years, FEV1 % predicted = 75.08, reversibility = 18.69%, Asthma Control Questionnaire = 1.31) were randomized to 1 of the 4 treatment groups. MF/F increased the time to first asthma deterioration thus decreasing the proportion of subjects experiencing asthma deterioration during the study (MF/F = 16.5%; versus MF = 28.2% [P = 0.006]; versus F = 44.7% [P < 0.001]; and vs placebo = 45.7% [P < 0.001]). Mean FEV1 AUC0–12h over baseline at week 12 were MF/F = 4.00 L × h; MF = 2.53 L × h; F = 3.83 L × h; and placebo = 1.11 L × h. Low rates of AEs were observed and were similar between treatment arms.ConclusionsIn asthmatics previously treated with low-dose ICS with or without a LABA, MF/F 100/10 μg BID was more effective than placebo, MF, or F (all administered by MDI) in reducing asthma deteriorations and improving lung function.

191 Quality of Life Improvements in Persistent Asthma Subjects Receiving Combined Mometasone Furoate and Formoterol

BackgroundA major goal of asthma treatment is to improve patients' health-related quality of life (QoL). Mometasone furoate/formoterol (MF/F) combination therapy was recently approved for the treatment of persistent asthma. The objective of this analysis was to examine the effect of MF/F on health-related QoL at the approved doses.MethodsData from 2 phase III studies investigating the effects of MF/F 200/10 μg (study P04334) and MF/F 400/10 μg (study P04431) were included. All subjects were ≥12 yeara and not well controlled on medium dose (P04334) or high-dose (P04431) inhaled corticosteroid (ICS). After 2 to 3 weeks of run-in on twice-daily (BID) MF 200 μg (P04334) or 400 μg (P04431), subjects were randomized to 26 weeks of BID MF/F 200/10 μg, MF 200 μg, F 10 μg, or placebo (PBO) in P04334; or 12 weeks of BID MF/F 200/10 μg, MF/F 400/10 μg, or MF 400 μg in P04431. The Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ [S]), consisting of 4 domains (Symptoms, Activity Limitation, Emotional Function, and Environmental Stimuli), was used to assess QoL. AQLQ(S) score changes from baseline were assessed; a difference ≥0.5 was considered clinically meaningful. Study protocols were approved by IRBs; written informed consent was provided by all subjects or a parent/guardian.ResultsIn P04334 (n = 781), subjects receiving MF/F 200/10μg experienced significant improvements in total score (13.1%) and the 4 domain scores of the AQLQ (S) at endpoint vs those receiving PBO (P ≤ 0.005) or F 10 μg (P ≤ 0.024). Clinically meaningful improvements in total AQLQ (S) from baseline to week 26 were observed in patients receiving MF/F 200/10 μg (0.61). In P04431 (n = 728), subjects receiving MF/F 200/10 μg experienced significant improvements in total score (12.8%) and the Symptoms and Activity Limitation domain scores of the AQLQ (S) at endpoint vs those who received MF 400 μg (P ≤ 0.017). Clinically meaningful improvements in total AQLQ (S) from baseline to week 12 occurred in patients receiving MF/F 200/10 μg (0.61), MF/F 400/10 μg (0.51), or MF 400 μg (0.5).ConclusionsPatients with persistent asthma receiving MF/F had statistically significant, clinically meaningful improvements in QoL in 2 phase III studies. These data suggest that MF/F combination therapy improves the health-related QoL of patients with persistent asthma who are inadequately controlled on medium- or high-dose ICS.

Clinical Efficacy and Safety of Combined Mometasone Furoate and Formoterol in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Clinical studies have shown that combining inhaled corticosteroids with long-acting β2-agonists can be effective in COPD. We evaluated the combination mometasone furoate/formoterol (MF/F), administered via metered-dose inhaler, as treatment for moderate-very severe COPD.

190 Effect of Mometasone Furoate/Formoterol Combination Therapy on Nocturnal Awakenings in Subjects With Persistent Asthma

BackgroundAsthmatics often report asthma-related nocturnal awakenings. These sleep interruptions may have a significant impact on patients' quality of life. We characterized the effect of mometasone furoate/formoterol (MF/F) administered via pressured metered-dose inhaler on incidence of nocturnal awakenings requiring short-acting β2-agonists (SABAs).MethodsMF/F's effect on nocturnal awakenings requiring SABA was characterized across 3 phase III efficacy trials (baseline = number of nights with awakenings in week before first dose; endpoint = number of nights/wk with awakenings averaged across the 26-week treatment period). Subjects were asthmatics previously treated with low- (n=746), medium- (n=781) or high-dose (n=728) inhaled corticosteroids at various doses. Subjects in the MF/F 100/10 μg BID study were randomized to 26 weeks of twice-daily (BID) treatment with MF/F 100/10 μg, MF 100 μg, F 10 μg, or placebo; subjects in the MF/F 200/10 μg BID study to 26 weeks of BID treatment with MF/F 200/10 μg, MF 200 μg, F 10 μg, or placebo; and subjects in the MF/F 400/10 μg BID study to 12 weeks of BID treatment with MF/F 400/10 μg, MF/F 200/10 μg, or MF 400 μg. All treatments were delivered via a metered dose inhaler.ResultsBaseline awakenings ranged from 0.84–1.05, 1.05–1.26, and 1.33–1.61 nights/wk in the MF/F 100/10 μg BID, MF/F 200/10 μg BID, and MF/F 400/10 μg BID studies, respectively. In the MF/F 100/10 μg BID study, nocturnal awakenings were reduced by MF/F = –0.42, MF = –0.21, F = –0.21, and placebo = 0.14 nights/wk; corresponding changes in the MF/F 200/10 μg BID study were –0.56, –0.35, +0.07 and 0.00 nights/wk, respectively. In each of these placebo-controlled studies, MF/F was superior to placebo (P < .001) and F (P ≤.035); MF was also superior to F and placebo. In the MF/F 400/10 μg BID study, awakenings were reduced by –0.70, –0.70 and –0.35 nights/wk by MF/F 200/10 μg, MF/F 400/10 μg, and MF 400 μg, respectively; both MF/F treatments were superior to MF (P ≤0.006).ConclusionsThese results provide evidence that validates the role of MF/F in reducing nocturnal asthma symptoms in patients with moderate to severe persistent asthma and supports the efficacy of MF/F compared with that of placebo and F.

187 Reduction in Asthma Deteriorations in Subjects with Persistent Asthma not Well Controlled on Low-, Medium-, or High-Dose Inhaled Corticosteroids

BackgroundWe present a post hoc analysis from 3 phase III clinical trials examining the effects of mometasone furoate/formoterol (MF/F) combination therapy on asthma deterioration in subjects previously not well controlled on low-, medium-, or high-dose inhaled corticosteroids (ICS).MethodsA 2- to 3-week run-in period with twice-daily (BID) MF 100 μg (MF/F 100/10 μg BID study), MF 200 μg (MF/F 200/10 μg BID study), or MF 400 μg (MF/F 400/10 μg BID study) was performed before subjects (aged ≥12 years) were randomized to BID: MF/F 100/10 μg, MF 100 μg, F 10 μg, or placebo for 26 weeks (n = 746; MF/F 100/10 μg BID study); MF/F 200/10 μg, MF 200 μg, F 10 μg, or placebo for 26 weeks (n = 781; MF/F 200/10 μg BID study); or MF/F 200/10 μg, MF/F 400/10 μg, or MF 400 μg for 12 weeks (n = 728; MF/F 400/10 μg BID study). Assessment of asthma deterioration (ie, 20% decrease in forced expiratory volume in 1 s [FEV1], 30% decrease in peak expiratory flow [PEF] on ≥2 consecutive days, or clinically judged deterioration [ie, emergency treatment, hospitalization, or treatment with excluded medications]) was a coprimary endpoint for the MF/F 100/10 μg BID and 200/10 μg BID studies and a secondary endpoint for the MF/F 400/10 μg BID study. Post hoc pair-wise comparisons of pooled MF/F vs pooled MF, F, and placebo treatment groups were performed.ResultsSample sizes in this pooled analysis were 861 for MF/F, 620 for MF, 390 for F, and 384 for placebo. There was a significantly lower incidence of asthma deterioration with MF/F (17.2%) versus MF (26.1%; P = 0.002), F (49.5%; P < 0.001), and placebo (50.8%; P < 0.001). Incidence of individual asthma deterioration criteria was 7.0% for MF/F, 10.0% for MF, 13.8% for F, and 17.7% for placebo for FEV1 reduction; 7.5%, 12.6%, 27.2%, and 26.3%, respectively, for PEF reduction; and 2.1%, 2.6%, 6.7%, and 5.2% for clinically judged deterioration.ConclusionsMF/F-treated subjects experienced a significantly lower rate of asthma deterioration compared with MF, F, and placebo in subjects previously not well controlled on low-, medium-, or high-dose ICS.

Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma

BackgroundMometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma.MethodsFollowing a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 μg (delivered as 2 inhalations of MF-MDI 100 μg) twice daily (BID), subjects (aged ≥12 y) were randomized to MF/F-MDI 200/10 μg BID (delivered as 2 inhalations of MF/F-MDI 100/5 μg) or FP/S administered via a dry powder inhaler (DPI) 250/50 μg (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV1 AUC0-12 h). Secondary assessments included onset of action (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient-reported outcomes.Results722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). Mean FEV1 AUC0-12 h change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L × h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]).ConclusionsThe results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints.Trial registrationClinicalTrials.gov: NCT00424008

The Long-term Safety Characteristics of Mometasone Furoate/Formoterol for the Treatment of Moderate to Very Severe Chronic Obstructive Pulmonary Disease: Pooled Findings From Two 1-Year Multicenter Clinical Trials

PURPOSE: The safety and tolerability profile associated with the long-term use of mometasone furoate/formoterol (MF/F) combination therapy administered via metered-dose inhaler for treatment of chronic obstructive pulmonary disease (COPD) has not been elucidated. We report pooled safety and tolerability findings from 2 independent 52-week clinical trials conducted to characterize the use of twice-daily (BID) inhaled MF/F 400/10µg and 200/10µg in moderate–very severe COPD.

Dose counter performance of mometasone furoate/formoterol inhalers in subjects with asthma or COPD

Consistent delivery of medication to treat asthma and chronic obstructive pulmonary disease (COPD) is critical for disease control. Dose tracking may eliminate the possibility of sub-therapeutic dosing. This study evaluated the overall performance, including accuracy and ruggedness, of the mometasone furoate/formoterol (MF/F) metered-dose inhaler (MDI) with an integrated numerical dose-counting mechanism in adolescent and adult subjects (aged ≥ 12 y) with persistent asthma or COPD. In a phase III, open-label, single-arm, multicenter study, subjects demonstrating at least 90% compliance with MF/F during the screening period received twice daily MF/F MDI 100/10 μg with the integrated dose counter for 4 weeks. Accuracy and ruggedness of the dose counter were assessed by the overall discrepancy rate of subject-recorded actuations versus subject-recorded dose counter readings. Discrepancy rates for Counterstrip™, a manual counting method, were evaluated for reference. Compliance and ergonomic safety were also assessed. The 233 subjects who used ≥ 90% of labeled actuations were included in the primary analysis. Of 26,317 total actuations, 33 dose counter discrepancies occurred (rate = 0.13/100 actuations), of which 13 were due to undercounting. In comparison, the Counterstrip discrepancy rate was 10-fold higher (1.34/100 actuations). Compliance with medication use, Counterstrip use, and e-diary recordings were all high (>98%). No new repetitive strain injuries or exacerbations of preexisting ergonomic injuries of the finger, hand, or arm were reported. The MF/F MDI dose counter was accurate and rugged in subjects with asthma or COPD. No new repetitive strain injuries or exacerbations of existing ergonomic injuries were associated with inhaler use. ClinicalTrials.gov identifier = NCT00604500.

Greater Reduction in Asthma Symptom Frequency During Treatment With Mometasone Furoate/Formoterol Combination Versus Monocomponents and Placebo

RATIONALE: The detrimental effect of asthma symptoms on patients' lives makes symptom reduction an important asthma therapy goal. We investigated the effectiveness of mometasone furoate/formoterol (MF/F) combination therapy in reducing asthma symptoms in subjects with persistent asthma uncontrolled on inhaled corticosteroids (ICS).

Efficacy and safety of medium and high doses of mometasone furoate/formoterol (MF/F) combination treatment in subjects with severe persistent asthma

Background Multiple strengths of mometasone furoate/formoterol (MF/F) MDI combination therapy are under investigation as new treatments for asthma. We report efficacy/ safety findings from a 3-month MF/F study in subjects with severe asthma. Materials and methods This was a 3-month, randomized, double-blind, parallelgroup, multicenter study with a 2-3-week open-label, run-in period of mometasone furoate (MF) 400 μg twice-daily (BID). Subjects (≥12 years) were randomized to MF/F (200/10 μg or 400/10 μg BID) or MF (400 μg BID). The primary endpoint was the area under the curve (AUC) of the change in serial FEV1 (0-12 hours) for MF/F 400/10 μg vs MF 400 μg from baseline to Week 12. Adverse events (AEs) and other clinical safety measures were recorded. Results A total of 728 subjects (mean: age = 47.9 y, asthma duration = 14.0 y, FEV1 % predicted = 66.3, reversibility = 22.9%, Asthma Control Questionnaire [ACQ] score = 1.93) were randomized. Improvements in mean changes from baseline in FEV1 AUC0-12 h (L ×h ) at Week 12 were MF/F 200/10 μg = 3.59, MF/F 400/10 μg = 4.19, and MF 400 μg = 2.04, with both MF/F doses significantly better than MF (p < 0.001). These FEV1s correspond to average hourly increases of 0.30, 0.35, and 0.17 L, respectively. MF/F was associated with rapid (<5 min) and sustained improvement in lung function. The percentage of subjects experiencing asthma deterioration (ie, severe asthma exacerbation) was 12.4% (MF/F 200/10 μg), 12.2% (MF/F 400/10 μg), and 18.3% (MF 400 μg). There were no notable differences in AEs between the groups. Conclusions Both medium- and high-dose MF/F combination therapy led to significantly greater improvements in lung function compared with high-dose MF monotherapy in severe asthmatics.

Non-inferiority efficacy comparison of mometasone furoate/formoterol versus fluticasone propionate/salmeterol combination therapies in subjects with persistent asthma

Background Mometasone furoate/formoterol (MF/F) combination therapy is a new treatment for persistent asthma. We report findings from a non-inferiority study that compared effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma.

Long-Term Safety of Mometasone Furoate/Formoterol Combination for Treatment of Patients with Persistent Asthma

Objective: The combination of inhaled corticosteroid (ICS) and long-acting β2-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS. Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC0−24 h) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored. Results: The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC0−24 h observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2–6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use. Conclusions: One-year treatment with the new combination therapies – twice-daily MF/F-MDI 200/10 and 400/10 μg – is safe and well tolerated in patients with persistent asthma.