daily.
The trials were dose-ranging trials of fluticasone propionate MDPI not designed to providecomparative effectiveness data and should not be interpreted as evidence of superiority/inferiority to fluticasone propionate inhalation powder. The metered doses forfluticasone MDPI (16, 28, 59, 118, 225, 434 mcg) used in Trial 201 and Trial 202 (see Figure 1)are slightly different from the metered doses for the comparator products (fluticasone inhalationpowder) and the Phase 3 investigational products which are the basis of the proposed commerciallabeled claim (55, 113, 232 mcg for fluticasone). The changes in doses between Phase 2 and 3
resulted from optimization of the manufacturing process.Figure 1: Baseline Adjusted Least Square Mean Change in Trough Morning FEV1 (L)
over 12 weeks (FAS)aFAS = full analysis set; aTrials were not designed to provide comparative effectiveness data and should not be
interpreted as superiority/inferiority to fluticasone propionate inhalation powderThe efficacy and safety of four doses of salmeterol xinafoate were eva luated in a double blind, 6-period crossover study compared with single dose fluticasone propionate MDPI and open labelfluticasone propionate/salmeterol 100/50 mcg dry powder inhaler (DPI) as comparator inpatients with persistent asthma. The trials were dose-ranging trials of the salmeterol componentof fluticasone propionate/salmeterol MDPI and not designed to provide comparativeeffectiveness data and should not be interpreted as evidence of superiority/inferiority tofluticasone propionate/salmeterol inhalation powder. The salmeterol doses studied were 6.8 mcg,13.2 mcg, 26.8 mcg and 57.4 mcg in combination with fluticasone propionate 118 mcg delivered by MDPI (expressed as metered dose). The metered doses for salmeterol (6.8, 13.2, 26.8, 57.4mcg) used in this study are slightly different from the metered doses for the comparator products(fluticasone/salmeterol inhalation powder) and the Phase 3 investigational products which are thebasis of the proposed commercial labeled claim (55, 113, 232 mcg for fluticasone and 14 mcg forsalmeterol). The phase 3 and commercial products were optimized to better match the strengths
to the comparators. Plasma for pharmacokinetic characterization was obtained at each dosingperiod. Fluticasone propionate/salmeterol xinafoate MDPI 118/13.2 mcg had similar clinicalefficacy with lower systemic exposure when compared to the 50 mcg of salmeterol in fluticasonepropionate/salmeterol 100/50 mcg dry powder inhaler (Figure 2).
Figure 2: Mean Baseline Adjusted FEV1 (mL) over 12 Hours (FAS)a
FS MDPI = fluticasone propionate/salmeterol multidose dry powder inhaler: Fp MDPI = fluticasone propionatemultidose dry powder inhaler; FS DPI = fluticasone propionate/salmeterol dry powder inhaler; FAS = full analysisset; FEV1 = forced expiratory volume in 1 second; aTrial was not designed to provide comparative effectiveness dataand should not be interpreted as superiority/inferiority to fluticasone propionate/salmeterol inhalation powder.
14.2 Trials in the Treatment of Asthma
Adult and Adolescent Patients Aged 12 Years and Older:Two 12-week randomized, double-blind, placebo-control, parallel-group, global Phase 3 clinicaltrials (Trials 1 and 2) were conducted in 1375 adult and adolescent patients (aged 12 years andolder, with baseline FEV1 40% to 85% of predicted normal) with asthma that was not optimallycontrolled on their current |
