Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) versus twice-daily inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) in patients with uncontrolled asthma: An open-label, randomized, controlled trial.

BACKGROUND: A variety of different fixed-dose combinations of inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) are available for the treatment of asthma. The aim of this 24-week, open-label, multicenter, Phase IIIb randomized controlled trial was to evaluate the efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI; 100/25 or 200/25 µg) compared with twice-daily fixed combinations of ICS/LABA (fluticasone propionate/salmeterol [FP/S] and budesonide/formoterol [BUD/F]) as maintenance therapy in patients with uncontrolled asthma treated with ICS alone. METHODS: Adult patients with documented physician-diagnosed asthma ≥1 year with an Asthma Control Test (ACT) score ≥15 and < 20 were included. The primary study endpoint was change from baseline in ACT total score at Week 12. RESULTS: Overall, 423 patients were randomized to receive study medication in France and Germany. The least-squares mean change (standard error) in ACT total score at Week 12 was 3.6 units with FF/VI and 2.8 with usual ICS/LABA, giving a treatment difference of 0.8 (95% confidence interval 0.1, 1.5; p = 0.033). Non-inferiority of FF/VI to usual ICS/LABA was confirmed at Weeks 6, 18 and 24. The observed safety profile for FF/VI in this study was in line with previous experience with FF/VI. CONCLUSIONS: These findings suggest that, in a tightly controlled randomized controlled trial setting, once-daily FF/VI provides similar asthma control over 24 weeks to usual, twice-daily ICS/LABA in patients with asthma that is uncontrolled on ICS alone. FF/VI was well tolerated.

The efficacy and safety of the novel long-acting ß2 agonist vilanterol in patients with COPD: a randomized placebo-controlled trial.

BACKGROUND: Vilanterol (GW642444M) (VI) is a novel, inhaled, long-acting ß(2) agonist with inherent 24-h activity under development as a once-daily combination therapy with an inhaled corticosteroid for COPD and asthma. This study assessed the dose response, efficacy, and safety of VI at doses of 3 to 50 µg in patients with moderate to severe COPD. METHODS: Six hundred two patients (intent-to-treat) were randomized (double-blind) to VI 3, 6.25, 12.5, 25, or 50 µg or placebo once daily for 28 days. The primary end point was change from baseline in trough FEV1 at the end of the 28-day treatment period. Secondary end points included 0- to 24-h weighted mean FEV(1) on days 1 and 28 and time to increases of ≥ 100 mL or ≥ 12% from baseline FEV(1) on day 1. Safety assessments included adverse events, vital signs, ECG assessment, and clinical laboratory tests. RESULTS: VI once daily for 28 days significantly improved trough FEV(1) in a dose-dependent manner vs placebo. Clinically relevant treatment differences of ≥ 130 mL in trough and 0- to 24-h weighted mean FEV(1) were observed with VI 25- and 50-µg doses vs placebo. All doses of VI were associated with a low incidence of treatment-related adverse events/serious adverse events, with no suggestion of effects on BP, pulse rate, QT intervals corrected for heart rate calculated by Fridericia formula, or blood glucose and potassium levels. CONCLUSIONS: VI 25 and 50 µg once daily provided both statistically and clinically relevant 24-h improvements in lung function in patients with COPD compared with placebo. All doses of VI had a safety and tolerability profile similar to placebo.

Add-on salmeterol compared to double dose fluticasone in pediatric asthma: a double-blind, randomized trial (VIAPAED).

RATIONALE: In asthmatic children whose symptoms are uncontrolled on standard doses of inhaled corticosteroids (ICS), guidelines recommend to either increase the ICS dose or to add further controller medication, e.g. a long acting ss2-agonist (LABA). The aim of this study was to compare the efficacy and safety of doubling the dose of ICS (fluticasone proprionate FP 200 microg twice daily) with adding a long-acting beta-2 agonist to the ICS (SFC, salmeterol 50 microg/ FP 100 microg twice daily) in children with uncontrolled asthma. METHODS: Children between 4 and 16 years of age were eligible for this multicenter, randomized, double blind, double dummy, parallel-group study. During a 14-day run-in phase, all children inhaled FP 100 microg b.i.d. Patients with persistent symptoms on > or =7 of 14 days were randomized to 8 weeks treatment with a Diskus(R) containing either SFC 50 microg/100 microg b.i.d. or FP 200 microg b.i.d.. The primary endpoint was the mean change in morning (a.m.) PEF from baseline. The initial statistical hypothesis of non-inferiority of SFC vs. FP was confirmed in an adaptive interim analysis, so that the study was terminated prematurely. RESULTS: 441 patients from 39 centers entered the run-in phase, and 64% of these were randomized to treatment (N = 138 to SFC and N = 145 to FP). After 8 weeks, patients on SFC had significantly better results for primary and secondary endpoints: The mean increase in morning PEF was 30.4 +/- 34.1 L/min in the SFC group and 16.7 +/- 35.8 L/min in the fluticasone group, and the mean (95% CI) improvement from baseline a.m. PEF in the ITT group was significantly larger after SFC (+8.6 L/min, CI: [1.3; infinity]). Patients in the SFC group experienced 8.7% (CI: [1.2;16.3]) more days without asthma symptoms and 8.0% (CI: [0.6;15.3]) more days without salbutamol than patients receiving FP. Good asthma control was achieved for a longer period in the SFC (3.4 +/- 2.7 weeks) group than in the FP group (2.7 +/- 2.7, P = 0.02). Both treatments were generally well tolerated. Asthma exacerbations were recorded in 3 and 6 and SAEs in 2 and 1 patients from the SFC and FP groups, respectively. CONCLUSIONS: In children with persistent asthma inadequately controlled on low dose ICS alone, adding a long acting beta-2-agonist to ICS in a single inhaler was more effective than doubling the ICS dose. These results support recommendations of adding LABA to low-dose ICS as the preferred controller option for children older than 4 years with symptomatic asthma.