A study was done to compare the efficacy and safety of the coprescription of salmeterol 50 microgram twice daily or 100 microgram twice daily with beclomethasone dipropionate (BDP) 500 micrograms twice daily (SALM 50 and SALM 100) with BDP 1,000 microgram twice daily (BDP 1,000) in patients with asthma not controlled by BDP 500 microgram twice daily (or the equivalent). Following a run-in period, 738 patients at 72 centers were randomized to treatment for 24 wk in a double-blind, parallel-group study during which they maintained a daily record of peak expiratory flow rates (PEFRs) and symptom scores. At about 40 of the centers, bronchial hyperresponsiveness (BHR) to histamine was measured during and at 3 and 14 d after stopping treatment. Both groups taking salmeterol showed an improvement of more than 45 L/min in their morning PEFR and 30 L/min in their evening PEFR, compared with respective improvements of 16 L/min and 6 L/min in the group taking BDP 1,000. Both the SALM 50 and SALM 100 groups had a significantly increased percentage of symptom-free and rescue-free days and nights compared with the BDP 1,000 group, and there was no difference between the two salmeterol groups. None of the treatments altered BHR. Exacerbation rates did not differ among the three groups. We conclude that in this selected group of symptomatic patients taking BDP 500 micrograms twice daily, the addition of salmeterol provides better improvement in lung function and symptom control, without altering BHR or increasing exacerbation rates, than does doubling the dose of BDP.

GlaxoSmithKline.

Background:The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS.Methods:In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment.Results:Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (−37 mL; 95% CI, −88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events.Conclusions:The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified.Trial registry:ClinicalTrials.gov; No.: NCT01147848; URL: www.clinicaltrials.gov

The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β2 agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma.Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. Co-primary end-points were change from baseline in trough forced expiratory volume in 1 s (FEV1) weighted mean (wm) 0–24 h serial FEV1. Secondary end-points included change from baseline in percentage of rescue-free 24-h periods, percentage of symptom-free 24-h periods and total Asthma Quality of Life Questionnaire (AQLQ). Safety assessments included adverse events, 24-h urinary cortisol excretion, vital signs and ECG.FF/VI significantly improved trough FEV1 and wmFEV1 versus FF and FP. Significantly more rescue-free and symptom-free 24-h periods were reported with FF/VI versus FF. Treatment differences for AQLQ were not significant. Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG.FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.

ClinicalTrials.gov; No.: NCT01752114; URL: www.clinicaltrials.gov).