Comparative Meta-Analysis of the Efficacy of Once-Daily Fluticasone Furoate 100 µG Versus Twice-Daily Fluticasone Propionate 250 µG in Adolescents and Adults with Persistent Asthma

Fluticasone furoate and fluticasone propionate are recommended options for prophylactic maintenance treatment of persistent asthma. Using data from two previous clinical studies (GSK studies: FFA109685/NCT00603278, FFA112059/NCT01159912), this meta-analysis compared change from baseline in clinic visit mean trough forced expiratory volume in 1 s (FEV₁) with fluticasone furoate 100 µg once-daily (FF100) versus fluticasone propionate 250 µg twice-daily (FP250) in adolescents and adults with persistent asthma. Using a DerSimonian–Laird random-effects model (primary meta-analysis), there was no statistically significant difference between FF100 and FP250 in change from baseline in trough FEV₁ (?1.7 mL [95% CI ?80.4, +77.0], p = 0.9664) and FF100 was non-inferior to FP250. Supporting analyses using least squares mean and fixed-effects model approaches produced similar findings. In this analysis, FF100 and FP250 demonstrated a comparable treatment effect on trough FEV₁ in patients aged ≥12 years with persistent asthma; however, results interpretation should consider study design and methodological limitations.     

Fluticasone furoate/vilanterol once daily improves night-time awakenings in asthma patients with night symptoms: Post hoc analyses of three randomized controlled trials

Objective: Symptoms, including night-time awakenings, affect the quality of life of people with asthma. Fluticasone furoate/vilanterol (FF/VI) reduces exacerbations, improves lung function, and rescue-free and symptom-free 24-hour periods in patients with asthma. These post hoc analyses compared daytime and night-time symptoms in patients with asthma who received FF/VI, versus FF, fluticasone propionate (FP) or placebo.

Methods: Daytime and night-time symptoms were collected via electronic daily diary cards in three Phase III randomized studies of once-daily FF/VI in patients with uncontrolled asthma on inhaled corticosteroids (ICSs) ± long-acting beta₂ agonists (n = 609/1039/586).

Endpoints included change from baseline in symptom-free days and nights (analyzed by Analysis of Covariance, covariates: baseline, region, sex, age, and treatment), time for patients to achieve seven consecutive symptom-free nights (analyzed by Cox proportional hazards' model, covariates as above), and proportion of patients experiencing 100% symptom-free nights per week (analyzed by logistic regression, covariates: percentage of symptom-free nights, sex, age, and treatment).

Results: Improvements in symptom-free days and nights were generally observed for all treatments. More patients who received FF/VI experienced 100% symptom-free nights in the last week of the treatment period than patients who received ICS alone or placebo. FF/VI also reduced time to achieve seven consecutive symptom-free nights. Patients with at least one night of symptoms at baseline experienced an additional 2.7 and 2.0 symptom-free nights per week with FF/VI 100/25 µg, versus 1.9 and 1.7 with FF alone; similar findings were seen with FF/VI 200/25 µg.

Conclusions: Benefits in terms of symptom-free days and nights were observed for patients receiving FF/VI versus comparators in these post hoc analyses.     

Efficacy and Safety of Umeclidinium Added to Fluticasone Propionate/Salmeterol in Patients with COPD: Results of Two Randomized, ­Double-Blind Studies

Combinations of drugs with distinct and complementary mechanisms of action may offer improved efficacy in the treatment of chronic obstructive pulmonary disease (COPD). In two 12-week, double-blind, parallel-group studies, patients with COPD were randomized 1:1:1 to once-daily umeclidinium (UMEC; 62.5 μg and 125 μg) or placebo (PBO), added to twice-daily fluticasone propionate/salmeterol (FP/SAL; 250/50 μg). In both studies, the primary efficacy measure was trough forced expiratory volume in 1 second (FEV₁) at Day 85. Secondary endpoints were weighted-mean (WM) FEV₁ over 0–6 hours post-dose (Day 84) and rescue albuterol use. Health-related quality of life outcomes (St. George's Respiratory Questionnaire [SGRQ] and COPD assessment test [CAT]) were also examined. Safety was assessed throughout. Both UMEC+FP/SAL doses provided statistically significant improvements in trough FEV₁ (Day 85: 0.127–0.148 L) versus PBO+FP/SAL. Similarly, both UMEC+FP/SAL doses provided statistically-significant improvements in 0–6 hours post-dose WM FEV₁ versus PBO+FP/SAL (Day 84: 0.144–0.165 L). Rescue use over Weeks 1–12 decreased with UMEC+FP/SAL in both studies versus PBO+FP/SAL (Study 1, 0.3 puffs/day [both doses]; Study 2, 0.5 puffs/day [UMEC 125+FP/SAL]). Decreases from baseline in CAT score were generally larger for both doses of UMEC+FP/SAL versus PBO+FP/SAL (except for Day 84 Study 2). In Study 1, no differences in SGRQ score were observed between UMEC+FP/SAL and PBO+FP/SAL; however, in Study 2, statistically significant improvements were observed with UMEC 62.5+FP/SAL (Day 28) and UMEC 125+FP/SAL (Days 28 and 84) versus PBO+FP/SAL. The incidence of on-treatment adverse events across all treatment groups was 37–41% in Study 1 and 36–38% in Study 2. Overall, these data indicate that the combination of UMEC+FP/SAL can provide additional benefits over FP/SAL alone in patients with COPD.     

Randomized,dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids

Objective: A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators. Methods: This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV₁). Blood samples were collected from a patient subset to evaluate pharmacokinetics. Adverse events were monitored. Results: Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV₁ over 12 weeks compared with placebo (p < 0.01). There were no substantial differences in FEV₁ change from baseline over 12 weeks between any Fp MDPI dose and Fp DPI 100 µg. Maximum observed concentration (C_max) of Fp increased with increasing Fp MDPI doses; time of C_max was similar across doses and treatments. Systemic exposures for Fp MDPI 25 and 50 µg were lower than that for Fp DPI 100 µg. The safety profile of Fp MDPI was consistent with that of Fp DPI. Conclusions: In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.     

Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized,Controlled, Cross-over Studies

Purpose

To compare the efficacy and safety of two long-acting dual bronchodilator combinations: indacaterol/glycopyrrolate (IND/GLY) versus umeclidinium/vilanterol (UMEC/VI).

Methods

Studies A2349 and A2350 were replicate, randomized, double-blind, double-dummy, active-controlled, cross-over studies in patients with moderate-to-severe COPD. Patients were randomized to sequential 12-week treatments of twice-daily IND/GLY 27.5/15.6 μg and once-daily UMEC/VI 62.5/25 μg, each separated by a 3-week washout. The primary objective was to demonstrate non-inferiority of IND/GLY compared with UMEC/VI in terms of the 24-h forced expiratory volume in 1 s profile at week 12 (FEV₁ AUC_0–24). Rescue medication use, symptom control, and safety were assessed throughout.

Results

Both treatments delivered substantial bronchodilation over 12 weeks, with improvements in FEV₁ AUC_0–24h at week 12 of 232 and 185 mL for IND/GLY, and 244 and 203 mL with UMEC/VI in Studies A2349 and A2350, respectively. The primary efficacy objective of non-inferiority of IND/GLY relative to UMEC/VI was not met as the lower bound of the confidence interval for the LS treatment comparison was below the pre-specified non-inferiority margin of ?20 mL in both studies: ?26.9 and ?34.2 mL, respectively (LS mean between-treatment differences: ?11.5 and ?18.2 mL). Both drugs were well tolerated, with AE profiles consistent with their respective prescribing information.

Conclusions

IND/GLY and UMEC/VI provided clinically meaningful and comparable bronchodilation. Non-inferiority of IND/GLY to UMEC/VI could not be declared although between-treatment differences were not clinically relevant. The data support the use of IND/GLY as an efficacious and well tolerated treatment option in patients with COPD. (ClinicalTrials.gov NCT02487446 and NCT02487498)

     

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study

Background: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta₂-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years. Objective: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age. Methods: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records. Results: The children had previously received short-acting β₂-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group. Conclusions: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.     

Comparison of high-dose salmeterol/fluticasone and moderate-dose salmeterol/fluticasone plus low-dose mometasone in patients with severe persistent asthma

Background and objective: The effects of adding a second inhaled corticosteroid with a different particle size, compared with using an increased dose of a single inhaled corticosteroid, were assessed in patients with persistent asthma. Methods: This was an open‐label study of Japanese asthma patients over 20 years of age. After a 1‐month run‐in period, 36 patients with inadequate control while using salmeterol/fluticasone propionate 50/250 µg (SFC50/250) bd, were randomized to receive SFC50/500 bd or SFC50/250 plus mometasone 100 µg bd (SFC50/250/MF100) for 2 months. Results: Both treatments resulted in improvements in morning and evening PEF. There were no significant changes in FEV₁, maximum mid‐expiratory flow, maximum expiratory flow rate at 50%, maximum expiratory flow rate at 25% or exhaled NO (FENO) in the SFC50/500 group. On the other hand, there were significant improvements in FEV₁% (+12.2%, P = 0.0142), %maximum mid‐expiratory flow (+28.9%, P = 0.0181), %MEF50 (+32.4%, P = 0.0206) and %MEF25 (+30.3%, P = 0.0113) in the SFC50/250/MF100 group. The changes in FENO (?23.2% (P = 0.0157) in the SFC50/250/MF100 group and ?14.5% (not significant) in the SFC50/500 group) did not differ significantly between the groups. Conclusions: In patients with severe persistent asthma, addition of low‐dose mometasone to SFC50/250 improved spirometric parameters, FENO and PEF, while an increase in dose from SFC50/250 to SFC50/ 500 only improved PEF.     

Fluticasone/Formoterol Combination Therapy versus Budesonide/Formoterol for the Treatment of Asthma: A Randomized,Controlled, Non-Inferiority Trial of Efficacy and Safety

Objectives. The inhaled corticosteroid fluticasone propionate (fluticasone) and the long-acting β₂ agonist formoterol fumarate (formoterol) have been combined in a single aerosol inhaler fluticasone/formoterol (flutiform^®). This study compared the efficacy and safety of fluticasone/formoterol with the combination product budesonide/formoterol (Symbicort^® Turbohaler^®). Methods. A randomized, double-blind, double-dummy, multicenter, Phase 3 study comprising a 7- (±3) day screening, 2–4-week run-in, and 12-week treatment periods. Patients aged ≥12 years with moderate to severe persistent asthma for ≥6 months before screening and forced expiratory volume in one second (FEV₁) 50–80% predicted and ≥15% reversibility following salbutamol inhalation were randomized to fluticasone/formoterol 250/10 μg twice daily (n = 140) or budesonide/formoterol 400/12 μg twice daily (n = 139). Results. Fluticasone/formoterol was comparable to budesonide/formoterol with respect to the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. The LS mean treatment difference was ?0.044 L, with a lower 95% confidence interval (CI) greater than the pre-defined non-inferiority limit of ?0.2 L (95% CI: ?0.130, 0.043 L; p < 0.001). Non-inferiority was also demonstrated for the secondary endpoints mean change in FEV₁ from baseline (pre-dose) to 2 hours post-dose at Week 12, and discontinuations due to lack of efficacy. Similar results were obtained for both treatment groups for all other secondary endpoints. Fluticasone/formoterol had a good safety profile that was comparable with budesonide/formoterol. Conclusions. This study demonstrated comparable efficacy of fluticasone/formoterol to budesonide/formoterol in terms of the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. This was supported by comparable results for both treatments for all secondary endpoints.     

Salmeterol/fluticasone combination in the treatment of COPD

Clinical trials of a combination therapy of an inhaled corticosteroid, fluticasone propionate (FP), with a long-acting β₂-agonist, salmeterol (Sal), have demonstrated a greater improvement in lung function and in quality of life measures after the combination compared with either component of alone. In a subanalysis of the data of the TRISTAN study, Sal/FP reduced exacerbation rates in COPD patients with a baseline FEV₁<50% of predicted. A combination therapy of budesonide and formoterol improved quality of life and FEV₁, and reduced exacerbations better than either component alone. In studies of FP or of Sal/FP in COPD, there was a reduction in all-cause mortality by 25% relative to placebo. Sal/FP has anti-inflammatory effects in COPD airways. FP inhibits markers of systemic inflammation, and it is not known whether Sal/FP has an advantage over FP alone. While long-acting β₂-agonists such as Sal can be recommended for treatment of moderate COPD, addition of inhaled steroid therapy such as FP should be considered in more severe disease.     

Effects of regular treatment with combination of salmeterol/fluticasone propionate and salmeterol alone in cough variant asthma

Objective: Cough variant asthma (CVA) is an important cause of chronic cough, and pathophysiological features of the disease appear to be similar to typical asthma. Because CVA is recognized as a precursor of asthma, early intervention with long-term anti-inflammatory agents may be recommended. However, the role of combination therapy with inhaled corticosteroid and β₂-agonist in the treatment of CVA has not been elucidated. To evaluate the effectiveness of the combination therapy, we investigated the clinical impact of regular treatment with salmeterol/fliticasone propionate combination (SFC) and inhaled salmeterol (SAL) alone in patients with CVA. Methods: The study was a randomized, controlled, parallel-group multi-center trial. Forty-three CVA patients were assigned to SFC (50/100?µg once daily) or SAL (50?µg twice daily) for 12 weeks. Then, these medications were stopped for the next 24 weeks. Main outcome measures were cough symptoms, pulmonary function and airway inflammation. Results: Treatment with each of SFC and SAL significantly decreased cough scores and increased FEV₁ and PEF, where the efficacy was more pronounced with SFC than SAL. SFC also decreased sputum eosinophil counts and eosinophil cationic protein contents, whereas SAL had no effect. After discontinuation of the treatment, cough scores increased, pulmonary function and eosinophilic airway inflammation were aggravated and returned to the baseline levels. Conclusions: Maintenance therapy with SFC provides further improvements in cough symptoms, pulmonary function and airway inflammation, and discontinuation of the therapy causes worsening of the disease, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with CVA.     

Efficacy and Safety of Fluticasone Propionate/Salmeterol HFA 134A MDI in Patients with Mild‐to‐Moderate Persistent Asthma

The objective of this study was to compare the efficacy and safety of fluticasone propionate (FP) (44 µg)/salmeterol (21 µg) delivered as two inhalations twice daily via a single hydrofluoroalkane (HFA 134a) metered dose inhaler (MDI) (FSC) with that of placebo HFA 134a (PLA), fluticasone propionate 44 µg chlorofluorocarbon (CFC) alone and salmeterol 21 µg CFC alone (S) in patients (n = 360) with persistent asthma previously treated with β₂‐agonists (short‐ or long‐acting) or inhaled corticosteroids (ICS). After 12 weeks of treatment, patients treated with FSC had a significantly greater increase (p ≤ 0.006) in mean FEV₁ AUC(bl) compared with PLA, FP, or S. At end point, mean change from baseline in morning predose FEV₁ for FSC (0.58 L) was significantly (p ≤ 0.004) greater than PLA (0.14 L), FP (0.36 L), and S (0.25 L). Patients treated with FSC also had a significantly higher probability of remaining in the study without being withdrawn due to worsening asthma (2%) compared with those in the PLA (29%) and S (25%) groups (p < 0.001). Finally, treatment with FSC resulted in significantly (p ≤ 0.007) greater improvements in morning and evening peak expiratory flow, need for rescue albuterol, and asthma symptom scores compared with FP, S, and PLA. The safety profile of FSC was also similar to FP or S alone. Initial maintenance treatment of the two main components of asthma, inflammation, and smooth muscle dysfunction (e.g., bronchoconstriction), with FSC results in greater overall improvements in asthma control compared with treatment of either individual component alone.     

Fast onset of effect of budesonide/formoterol versus salmeterol/fluticasone and salbutamol in patients with chronic obstructive pulmonary disease and reversible airway obstruction

Background and objectives: Data on the onset of action of COPD medications are lacking. This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate‐to‐severe COPD and reversible airway obstruction. Methods: In this double‐blind, double‐dummy, crossover study, 90 patients (aged ≥40 years; FEV₁ 30–70% predicted) were randomized to a single dose (two inhalations) of budesonide/formoterol 160/4.5 μg, salmeterol/fluticasone 25/250 μg, salbutamol 100 μg or placebo (via pressurized metered‐dose inhalers) on four visits. The primary end‐point was change in FEV₁ 5 min after drug inhalation; secondary end‐points included inspiratory capacity (IC) and perception of onset of effect. Results: Budesonide/formoterol significantly improved FEV₁ at 5 min compared with placebo (P < 0.0001) and salmeterol/fluticasone (P = 0.0001). Significant differences were first observed at 3 min. Onset of effect was similar with budesonide/formoterol and salbutamol. Improvements in FEV₁ following active treatments were superior to placebo after 180 min (all P < 0.0001); both combinations were better than salbutamol at maintaining FEV₁ improvements (P ≤ 0.0001) at 180 min. Active treatments improved IC at 15 and 185 min compared with placebo (P < 0.0001). Maximal IC was greater with budesonide/formoterol than salmeterol/fluticasone (P = 0.0184) at 65 min. Patients reported a positive response to the perceptions of the onset of effect question shortly after receiving active treatments (median time to onset 5 min for active treatments vs 20 min for placebo), with no significant difference between active treatments. Conclusion: Budesonide/formoterol has an onset of bronchodilatory effect in patients with COPD and reversible airway obstruction that is faster than salmeterol/fluticasone and similar to salbutamol.     

The severity of airways obstruction as a determinant of treatment response in COPD

Guidelines recommend that patients with COPD are stratified arbitrarily by baseline severity (FEV₁) to decide when to initiate combination treatment with a long-acting β₂-agonist and an inhaled corticosteroid. Assessment of baseline FEV₁ as a continuous variable may provide a more reliable prediction of treatment effects. Patients from a 1-year, parallel-group, randomized controlled trial comparing 50 μg salmeterol (Sal), 500 μg fluticasone propionate (FP), the combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV₁ <50% and FEV₁ ≥50% predicted subgroups (n=949/513 respectively). Treatment effects on clinical outcomes – lung function, exacerbations, health status, diary card symptoms, and adverse events – were investigated. Treatment responses based on a pre-specified analysis explored treatment differences by severity as a continuous variable. Lung function improved with active treatment irrespective of FEV₁; Sal/FP had greatest effect. This improvement appeared additive in milder disease; synergistic in severe disease. Active therapy significantly reduced exacerbation rate in patients with FEV₁ <50% predicted, not in milder disease. Health status and breathlessness improved with Sal/FP irrespective of baseline FEV₁; adverse events were similar across subgroups. The spirometric response to Sal/FP varied with baseline FEV₁, and clinical benefits were not restricted to patients with severe disease. These data have implications for COPD management decisions, suggesting that arbitrary stratifications of baseline severity are not necessarily indicative of treatment efficacy and that the benefits of assessing baseline severity as a continuous variable should be assessed in future trials.     

Efficacy and safety of the long-acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD

Introduction: GSK233705 is a recently developed inhaled anticholinergic being investigated for the potential treatment of chronic obstructive pulmonary disease (COPD). Objectives: This dose‐ranging, parallel‐group, double‐blind study compared the bronchodilator efficacy, safety and pharmacokinetics of GSK233705 with placebo in patients with moderate‐to‐severe COPD. Methods: Patients were randomised to receive 12.5 µg, 25 µg, 50 µg, 100 µg or 200 µg of GSK233705 or placebo once daily for 28 days. The primary endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV₁) on day 29. Results: The intent‐to‐treat population consisted of 576 patients (mean predicted FEV₁ 51%; mean age 62 years). Treatment with GSK233705 produced statistically significant improvements in pulmonary function compared with placebo. Only the 200 µg dose exceeded the predefined target threshold of 130‐mL difference compared with placebo for the primary endpoint of change from baseline in trough FEV₁ on day 29. No clear pattern of dose response was observed for the other doses. Serial FEV₁ (0–24 h) showed a peak effect around 2 h postdose and tended to decline to clinically insignificant levels compared with placebo at 23 and 24 h. Each dose of GSK233705 was well tolerated. The incidence of adverse events was low and similar across all treatment groups. There were no clinically significant effects on laboratory parameters, vital signs or electrocardiograms. Conclusion: All doses of GSK233705 demonstrated bronchodilatory activity and were well tolerated. Although the onset of bronchodilation was rapid, it was not sustained over 24 h making it unsuitable for once‐daily dosing. Please cite this paper as: Bateman E, Feldman G, Kilbride S, Brooks J, Mehta R, Harris S, Maden C and Crater G. Efficacy and safety of the long‐acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD. Clin Respir J 2012; DOI:10.1111/j.1752‐699X.2011.00278.x.     

Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study

Inhaled indacaterol/glycopyrronium fixed-dose combination (IND/GLY) is approved in over 80 countries, including the EU, Japan, Australia and Switzerland and the US. The LANTERN study evaluated the efficacy of IND/GLY compared with inhaled long-acting β₂-agonist (LABA)/inhaled corticosteroid (ICS) or salmeterol/fluticasone (SFC) in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. Here we present the efficacy and safety of IND/GLY versus SFC in the Chinese cohort from the LANTERN study. LANTERN was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group study conducted in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. The patients were randomized (1:1) to once-daily IND/GLY (110/50 μg) or twice-daily SFC (50/500 μg). The primary endpoint was non-inferiority of IND/GLY versus SFC in terms of trough FEV₁. Of the total 744 patients randomized in the LANTERN study, 598 (80.4%) were from Mainland China and randomized to IND/GLY (n = 298) or SFC (n = 300), and 553 (92.5%) completed the study. IND/GLY showed superiority over SFC with a statistically significant and clinically meaningful improvement in trough FEV₁, FEV₁ AUC_0–4h, peak FEV₁ and trough forced vital capacity (FVC) change from the baseline. Annualized rate of moderate or severe COPD exacerbations was significantly lower (43%) with IND/GLY compared with SFC (rate ratio: 0.57, p = 0.015). Overall, adverse events were lower for IND/GLY (34.6%) versus SFC (43.1%). IND/GLY was superior in achieving bronchodilation versus SFC in a Chinese subgroup of patients from this study.

Clinicaltrials.gov identifier: NCT01709903     

A Short-Term Comparison of Fluticasone Propionate/Salmeterol with Ipratropium Bromide/Albuterol for the Treatment of COPD

Background: This is the first comparison of two combination therapies, fluticasone propionate/salmeterol and ipratropium bromide/albuterol (salbutamol), for the treatment of patients with COPD. Methods: A randomized, double-blind, double-dummy, parallel group, multicenter evaluation of fluticasone propionate/salmeterol 250/50µg twice daily via DISKUS® and ipratropium bromide/albuterol 36/206µg four times daily via metered-dose inhaler over 8 weeks was conducted at 41 research sites in the US. Morning pre-dose FEV₁, 6-hour serial spirometry, PEF, dyspnea, night-time awakenings, supplemental albuterol use, and patient diary evaluations of symptoms were evaluated. Results: A total of 365 patients with symptomatic COPD were enrolled. The treatment groups were similar in mean age (63.3 and 63.9 years), screening pulmonary function (44.1% and 43.2% of predicted FEV₁), race (96% and 95% White), and sex distribution (59% and 60% male). Both fluticasone propionate/salmeterol and ipratropium bromide/albuterol improved lung function, symptoms, and supplemental albuterol use compared with baseline. Fluticasone propionate/salmeterol was more effective than ipratropium bromide/albuterol for improvement in morning pre-dose FEV₁, morning PEF, 6-hour FEV₁ area under the curve (AUC₆), Transition Dyspnea Index® (TDI) focal score, daytime symptom score, night-time awakenings, sleep symptoms, and albuterol-free nights (p ≤ 0.013). Compared with day 1, at week 8 the FEV₁ AUC₆ significantly increased with fluticasone propionate/salmeterol and significantly decreased with ipratropium bromide/albuterol (p ≤ 0.003). The incidence of adverse events was similar between treatment groups, except for a higher incidence of oral candidiasis with fluticasone propionate/salmeterol. Conclusions: Short-term treatment with the combined inhaled corticosteroid and long-acting β₂-adrenoceptor agonist fluticasone propionate/salmeterol resulted in greater control of lung function and symptoms than combined ipratropium bromide/albuterol bronchodilator therapy, in patients with COPD.     

Early Bronchodilatory Effects of Budesonide/Formoterol pMDI Compared with Fluticasone/Salmeterol DPI and Albuterol pMDI: 2 Randomized Controlled Trials in Adults with Persistent Asthma Previously Treated with Inhaled Corticosteroids

Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged ≥18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 μ g, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 μ g × 2 inhalations (160/9 μ g), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 μ g × 1 inhalation, albuterol pMDI 90 μ g × 2 inhalations (180 μ g), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV₁) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV₁ within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.     

Safety,efficacy, and dose response of fluticasone propionate delivered via the novel MDPI in patients with severe asthma: A randomized,controlled, dose-ranging study

Objective: Evaluate fluticasone propionate (Fp) using a novel, inhalation-driven, multidose dry powder inhaler (MDPI) in patients with severe persistent asthma, versus placebo MDPI and Fp dry powder inhaler (DPI). Methods: Patients with persistent asthma despite use of high-dose inhaled corticosteroids were randomized to Fp MDPI 50, 100, 200, or 400 mcg; Fp DPI 250 mcg; or placebo MDPI twice daily for 12 weeks. The primary outcome measure was change from baseline in trough forced expiratory volume in 1 second (FEV₁) over the 12-week period, compared with placebo; secondary measures included change from baseline in peak expiratory flow (PEF), rescue inhaler use, and time to withdrawal due to meeting stopping criteria. Safety included adverse events and laboratory evaluations. Results: Six hundred forty patients were randomized; 459 (72%) completed the study. Numerical dose-related improvements in FEV₁ were observed in all Fp MDPI groups over 12 weeks but were not significantly greater versus placebo. Increases in morning PEF (baseline to week 12) were substantially greater than placebo in all Fp MDPI groups. The Fp MDPI and Fp DPI groups had substantial reductions in rescue inhaler use from baseline to end point versus placebo (p ≤ 0.05). Efficacy was comparable between Fp MDPI and Fp DPI. No new safety signals were detected; the safety profile of Fp MDPI was similar to that of Fp DPI. Conclusions: Clinical benefit observed with Fp MDPI in patients with persistent asthma was comparable to Fp DPI. Safety was reassuring with no unexpected findings. These results support further evaluation of Fp MDPI in asthma. (ClinicalTrials.gov identifier NCT01576718; EudraCT number 2010-023601-35).