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Chronic obstructive pulmonary disease (COPD) is a progressive disease in which patients become increasingly disabled by their symptoms and limited in their activities. Health-related quality of life may be profoundly impaired even in the early stages of the disease. Treatment with long-acting inhaled bronchodilators can improve lung function, symptoms and health status and reduce exacerbations of COPD. This review profiles the efficacy, safety and tolerability of indacaterol, an inhaled β2-agonist bronchodilator for once-daily maintenance treatment of patients with COPD. After 12 weeks of treatment with a once-daily dose of 75 µg (the dose approved in the USA and Canada) in patients with moderate to severe COPD, compared with placebo, indacaterol provided significant and clinically relevant levels of bronchodilation [difference in trough forced expiratory volume in 1 s: 131 ml; 95% confidence interval (CI) 104–159; p < 0.001], together with significant reductions in symptom scores (difference in transition dyspnea index total score: 0.84 points; 95% CI 0.37–1.31; p < 0.001) and improvements in health status (difference in St George’s Respiratory Questionnaire total score: −3.8 units; 95% CI −5.6 to −2.0; p < 0.001). The overall safety and tolerability of once-daily treatment with indacaterol 75 µg for 12 weeks did not differ in any substantial aspect from placebo treatment. Indirect comparisons analyzing pooled clinical data and meta-analyses suggest that treatment with indacaterol 75 µg once daily may be effective in reducing exacerbations of COPD, and that its effects on lung function and health status will be comparable with other currently available inhaled long-acting bronchodilators used for COPD. Treatment with indacaterol 75 µg once daily provides effective bronchodilation, improves dyspnea and health status, and has a well characterized profile of safety and tolerability.

SummaryBackgroundFluticasone furoate (FF)/vilanterol (VI) is a novel once-daily inhaled corticosteroid/long-acting β2-agonist combination therapy for COPD. We aimed to assess the efficacy and safety of two strengths of FF/VI (100/25 μg; 50/25 μg) vs. individual components (FF 100 μg, VI 25 μg) and placebo over 24 weeks.MethodsMulticentre, randomised, placebo-controlled, double-blind, parallel-group study of patients (N = 1030) with moderate-to-severe COPD. All medication was administered once daily in the morning. Co-primary efficacy endpoints were: (1) weighted mean (wm) FEV1 (0–4 h post-dose on day 168) to assess acute lung function effects; and (2) trough FEV1 (23–24 h post-dose on day 169) to assess long-lasting effects. Symptom-related outcomes were analysed and adverse events (AEs) assessed.ResultsMain findings were: (1) the combination of FF/VI at a strength of 100/25 μg significantly (p

Dennis E Doherty1, Donald P Tashkin2, Edward Kerwin3, Barbara A Knorr4, Tulin Shekar4, Sibabrata Banerjee4, Heribert Staudinger41Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3Clinical Research Institute of Southern Oregon, Medford, OR, 4Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USARationale: 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 (FEV1) over 0–12 hours (AUC0-12 h FEV1) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV1 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 AUC0-12 h FEV1 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 FEV1, for which effects were further investigated, excluding subjects whose AM FEV1 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.Keywords: COPD, FEV1, spirometry, exacerbation, inhaled corticosteroid, bronchodilator

Indacaterol is the first once-daily, long-acting, inhaled β(2)-agonist bronchodilator for maintenance treatment of chronic obstructive pulmonary disease (COPD). Two studies (previously reported in a Congress abstract) were performed in 2010 to provide efficacy and tolerability data to support the application for approval in the United States of indacaterol 75 μg once daily, a dose lower than that previously investigated in most studies.The primary objective was to evaluate the efficacy of indacaterol 75 μg once daily in terms of 24-hour post-dose ("trough") forced expiratory volume in the first second of respiration (FEV(1)) compared with placebo after 12 weeks of treatment.Patients with moderate to severe COPD were randomized to receive double-blind treatment with indacaterol 75 μg once daily (n = 163 and 159) or placebo (n = 160 and 159) for 12 weeks. In addition to trough FEV(1) after 12 weeks, rescue albuterol use, health status (St. George's Respiratory Questionnaire [SGRQ]), and tolerability were evaluated. Clinically relevant differences between active and placebo treatments were defined as ≥120 mL for trough FEV(1) and a decrease of ≥4 units in SGRQ total score.Of patients enrolled in the 2 studies, 54% were men, and 90% and 94% were white, with mean age 64 and 61 years. Mean duration of COPD was 7 years; smoking history was 52 pack-years; and 45% and 37% of patients were receiving inhaled corticosteroid therapy. At week 12, indacaterol demonstrated clinically relevant bronchodilator efficacy, increasing trough FEV(1) by ≥120 mL versus placebo (P0.001), with significant bronchodilation maintained at all time points from 5 minutes to 24 hours post-dose. Over 12 weeks, relative to placebo, in patients receiving indacaterol therapy, rescue albuterol use was reduced by 1.2 and 0.7 puffs per day (P0.01), and the percentage of rescue-free days was increased by 13.7 and 8.4 (P0.01). At week 12, the SGRQ total score differed in the indacaterol group versus the placebo group by -3.8 and -3.6, respectively (P ≤ 0.01). Adverse events were reported for 49% and 45% of patients receiving indacaterol therapy, and for 46% and 41% receiving placebo.Compared with placebo, indacaterol 75 μg once daily provided statistically significant and clinically relevant 24-hour bronchodilation and was well tolerated. In patients receiving indacaterol, the reduction in rescue albuterol use was statistically significant. Changes in health status also were statistically significant compared with placebo, although the differences of 3.6 and 3.8 units were below the predefined 4-unit level of clinical relevance. The results of these studies suggest that indacaterol 75 μg once daily is an effective maintenance treatment in patients with moderate to severe COPD. ClinicalTrials.gov identifiers: NCT01072448 and NCT01068600.

Inhaled corticosteroids (ICSs) are a first-line treatment for persistent asthma. This study was designed to compare the efficacy and safety of ciclesonide (CIC) in subjects with mild-to-moderate persistent asthma not using an ICS. This was a multicenter, double-blind, parallel-group, placebo-controlled, 16-week study in subjects who were > or =12 years old, had a > or =6-month history of persistent asthma, a forced expiratory volume in 1 second (FEV(1)) of > or =60 to < or =85% predicted, and who were not using an ICS < or =30 days before study entry. Subjects were randomized to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 170); CIC, 160 microg once daily in the morning (CIC160 q.d. in the A.M.; n = 173); CIC80 b.i.d. for 4 weeks followed by CIC160 q.d. for 12 weeks (CIC80 b.i.d./CIC160 q.d.; n = 171); or placebo (n = 177). Change in FEV(1) from baseline to the average of weeks 12 and 16 (primary end point) and to week 16, A.M. peak expiratory flow, rescue albuterol use, nighttime awakenings, asthma symptom scores, and safety were evaluated. FEV(1) improved from baseline to the average of weeks 12 and 16 for CIC80 b.i.d. (+0.30L; p < 0.0001), CIC160q.d. (+0.19L; p < 0.0001), CIC80 b.i.d./CIC160 q.d. (+0.19L; p < 0.0001), and placebo (+0.06L; p = 0.0251); improvement was greatest for CIC80 b.i.d. (p < 0.01). At week 16, all CIC treatments significantly improved FEV(1) and A.M. PEF from baseline (p < 0.0001) and compared with placebo (p < or = 0.015). All treatments reduced albuterol use and nighttime awakenings and improved asthma symptom scores (p < or = 0.05 versus baseline); these improvements were greater for CIC80 b.i.d. than for placebo (p < 0.01). The incidence of adverse events was similar among treatment groups (range, 53-58%). In this study, CIC80 b.i.d. improved disease control in subjects with mild-to-moderate persistent asthma not using an ICS and provided greater improvements than CIC160 q.d.

Corrigendum to “Efficacy and safety of umeclidinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: Results of two randomized studies” [Respir. Med. 109 (2015) 1155e1163] Thomas M. Siler a, , Edward Kerwin , Ana R. Sousa , Alison Donald , Rehan Ali , Alison Church d a Midwest Chest Consultants, PC, 330 First Capitol Drive, Suite 470, St Charles, MO, USA b Clinical Research Institute of Southern Oregon, Medford, OR, USA c GSK, Respiratory Medicines Development Centre, Stockley Park, Middlesex, UK d GSK, Respiratory and Immuno-Inflammation, Research Triangle Park, NC, USA

a Krefting Research Centre, University of Gothenburg, Box 424, SE 40530 Gothenburg, Sweden b Center for Genomics and Personalized Medicine, Wake Forest University School of Medicine, WinstonSalem, NC 27157, USA c Department of Medicine, University of Wisconsin, Madison, WI 53706, USA d Michael G DeGroote School of Medicine, Hamilton, Ontario L8S4L8, Canada e Institute of Inflammation and Repair, University of Manchester, University Hospital of South Manchester, Manchester M23 9LT, UK f Clinical Research Institute of Southern Oregon, Medford, OR 97504, USA g Respiratory Medicine Development Centre, GlaxoSmithKline, London UB11 1BT, UK h Quantitative Sciences Division, GlaxoSmithKline, Research Triangle Park, NC 27713, USA i Department of Medicine, University of Cape Town, Cape Town 7925, South Africa

SummaryObjectiveThe reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma.MethodsA 3-month, double-blind, placebo-controlled clinical trial (n=123), followed by a 9-month open-label phase (n=120). The study was conducted at 26 medical centers in the United States. Patients were randomized to treatment with MF-MDI 400 or 800μg twice-daily (bid) doses, or placebo in the double-blind trial. All patients received MF in the open-label phase.ResultsAt the endpoint of the double-blind trial, MF-MDI 400 and 800μg bid reduced the daily OCS dose by 39.4% and 31.1%, respectively, while placebo increased the OCS dose by 107.2% (P

Background Inhaled corticosteroids are recommended as first-line therapy for persistent asthma. Objective We sought to assess the efficacy and safety of ciclesonide once daily in patients with mild-to-moderate persistent asthma. Methods An integrated analysis of 2 identical, multicenter, double-blind, randomized, parallel-group, placebo-controlled trials was conducted. Patients (n = 1015; aged ≥12 years) with mild-to-moderate asthma (FEV 1 of 60% to 85% of predicted value) were randomized to ciclesonide 80 μg (CIC80), 160 μg (CIC160), or 320 μg (CIC320), once daily (exactuator doses) in the morning or placebo for 12 weeks. Results All ciclesonide groups showed significant improvements from baseline to week 12 in FEV 1 compared with the placebo group (CIC80, 0.12 L [ P = .0007]; CIC160, 0.13 L [ P = .0004]; and CIC320, 0.14 L [ P 1 percent predicted, morning and evening peak expiratory flow, 24-hour asthma symptom score, daily albuterol use, and nighttime awakenings were significantly improved in all ciclesonide groups compared with the placebo group. Overall ciclesonide safety profile and rates of oropharyngeal adverse events for all groups were low and similar to those of the placebo group. Fewer ciclesonide-treated patients exhibited asthma-aggravated adverse events, and fewer ciclesonide-treated patients discontinued the study for any reason or because of a lack of efficacy compared with those in the placebo group. No suppression of hypothalamic-pituitary-adrenal–axis function (as assessed by means of 24-hour urinary cortisol levels corrected for creatinine and peak serum cortisol levels after stimulation with low-dose [1 μg] cosyntropin) was observed with any dose of ciclesonide. Conclusions In this integrated analysis, ciclesonide once daily administered in the morning is effective and well tolerated.

Background For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines. Objective To compare montelukast, a oncedaily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting β-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year. Methods A randomized, doubleblind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 μg/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 μg/d) or montelukast (10 mg/d) for 48 weeks. Results Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated. Conclusions Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.

~6 Puffs per week difference; 31% decrease vs. placebo (p < 0.001) Safety and Efficacy of ARRY-502, a Potent, Selective, Oral CRTh2 Antagonist, in Patients with Mild to Moderate Th2-Driven Asthma Sally Wenzel1, Robert Hopkins2, Michael Saunders2, David Chantry2, Lisa Anderson2, Roger Aitchison2, Christine Eberhardt2, Stacie Bell2, Jeremy Cole3, James D. Wolfe4, Sheldon Spector5, Lawrence Sher6, Edward Kerwin7 and Laurence E. Burgess2 1University of Pittsburgh Asthma Institute, Pittsburgh, PA; 2Array BioPharma, Boulder, CO; 3IPS Research Company, Oklahoma City, OK; 4Allergy & Asthma Associates of Santa Clara County Research Center, San Jose, CA; 5California Allergy & Asthma Medical Group, Los Angeles, CA; 6Peninsula Research Associates, Rolling Hills Estate, CA; 7Clinical Research Institute of Southern Oregon, Medford, OR

Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy.We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy.We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily.FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable.Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.

T U E S D A Y 816 Effect of Inhaled Corticosteroids (ICS) Vs. Inhaled Corticosteroid with Long-Acting Beta2 Agonists (ICS/LABA) On Asthma Control: Results From National Asthma Survey Neetu Talreja, MD, Dennis K. Ledford, MD, FAAAAI, Richard F. Lockey, MD; Morsani College of Medicine University of South Florida and James A. Haley Veteran Hospital. RATIONALE: There is limited evidence for the comparative efficacy of ICS vs. ICS/LABA to treat asthma in children under 12 years. METHODS: Data from the 2003 National Asthma Survey were analyzed to compare asthma control in children (5 to 11 yrs) using ICS vs. ICS/LABA. Both short term (symptoms within last 2 weeks, day and night symptoms in last 30 days and use of systemic glucocorticoids in last 3 months) and long term (asthma exacerbation, emergency department visits, hospitalizations and activity limitations in the prior year) outcomes were compared. Demographics, availability of health insurance, indoor allergen exposure and asthma education were compared between the two groups. Asthma control in adult (18 to 44 years) and older population (>565 years) was also assessed for the same parameters. RESULTS: 134 children on ICS and 69 on ICS/LABA were identified. Baseline characteristics were similar in both groups. There were no differences in short and long term asthma outcomes between the two groups (p>0.05 for all outcome measures). Similar results were obtained with the adult and older population (p>0.05 for all outcome measures). ICS/LABAwas used for more than 6 months in 58% of children, 81% of adults and 46% of the older population. CONCLUSIONS: Asthma control in children using ICS vs. ICS/LABA was similar. So was asthma control using similar medications in the adult and older populations. LABA tolerance or the use of ICS/LABA in subjects with more severe asthma could explain these findings.

Introduction and objective Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist indicated for the treatment of chronic obstructive pulmonary disease (COPD). COPD is characterised by periodic worsening of symptoms (exacerbations) that are associated with increased morbidity and mortality. Here, we report the results of a pooled analysis of aclidinium on exacerbations. Methods Data from two Phase III studies (3-month ACCORD COPD I and 6-month ATTAIN) were included in this analysis . Both were designed to evaluate the efficacy and safety of aclidinium 200 µg and 400 µg (metered dose) BID versus placebo (primary endpoint: change from baseline in FEV1). Adults (aged ≥40 years) with moderate-to-severe COPD, who were current/former smokers with a smoking history ≥10 pack-years, were included. Exacerbations (additional endpoint) were assessed in both studies using healthcare resource utilisation (HCRU) criteria (increase in symptoms for ≥2 consecutive days that required increased medication use or other medical intervention) and, in ATTAIN only, with the Exacerbations of Chronic Pulmonary Disease Tool (EXACT [daily diary card data with exacerbations defined according to the developer’s criteria]). Neither study was individually powered to assess treatment differences in exacerbation frequency. In this pooled analysis, exacerbation rate ratios (per patient/year for aclidinium versus placebo) were analyzed using a Poisson regression model corrected for over-dispersion; 95% confidence intervals and p-values were calculated. Results Data for 1378 patients were included; the majority (62%) were male with a mean age of approximately 63 years. At baseline, >60% of patients were classed as GOLD stage II (moderate), and 31% reported ≥1 exacerbations in the previous 12 months. In both studies, there was a trend towards relative reduction (approximately 30%) in the rate of moderate or severe exacerbations (requiring antibiotic or corticosteroid treatment, or hospitalisation) with both aclidinium doses versus placebo ([F][1]igure). A significant reduction in moderate or severe exacerbation rate was observed with aclidinium 400 µg versus placebo when data from both studies were pooled (0.31 vs 0.44; rate ratio 0.71, p=0.01). ![Abstract P189 Figure 1][2] Abstract P189 Figure 1 Conclusions This pooled analysis provides evidence to support a reduction in moderate or severe COPD exacerbations with aclidinium 200 µg and 400 µg BID compared with placebo. [1]: #F1 [2]: pending:yes

Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Davis Gates5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR, USA; 4Fundación Salud Bosque, Bogota, Colombia, 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USABackground: 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 (FEV1), area under the curve from 0 to 12 hours postdose (AUC0–12 h), and morning predose/trough FEV1 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 FEV1 AUC0–12 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 FEV1 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