nts and standardized baseline-adjusted FEV1 AUEC0-12h at week 12 analyzed for a subsetof 312 patients who performed postdose serial spirometry.
Efficacy results in this trial were similar to those observed in Trial 1. Patients in both fluticasone
propionate/salmeterol MDPI groups had significantly greater improvements in trough FEV1
compared with the fluticasone propionate MDPI groups and the placebo group:
Fluticasone propionate/salmeterol MDPI 113/14 mcg: LS mean change of 0.271 L at12 weeks
Fluticasone propionate/salmeterol MDPI 232/14 mcg: LS mean change of 0.272 L at12 weeks
Fluticasone propionate MDPI 113 mcg: LS mean change of 0.119 L at 12 weeks
Fluticasone propionate MDPI 232 mcg: LS mean change of 0.179 L at 12 weeks, andPlacebo: LS mean change of -0.004 L at 12 weeks.
Estimated mean differences between:
Fluticasone propionate/salmeterol MDPI 113/14 mcg and fluticasone
propionate/salmeterol MDPI 232/14 mcg compared to placebo were 0.274 L (95% CI:0.189, 0.360) and 0.276 L (95% CI: 0.191, 0.361), respectively.
Fluticasone propionate MDPI 113 mcg and fluticasone propionate MDPI 232 mcgcompared to placebo were 0.123 L (95% CI: 0.038, 0.208) and 0.183 L (95% CI: 0.098,0.268), respectively.
Fluticasone propionate/salmeterol MDPI 232/14 mcg and fluticasone propionate MDPI232 mcg was 0.093 L (95% CI: 0.009, 0.178).
Fluticasone propionate/salmeterol MDPI 113/14 mcg and fluticasone propionate MDPI113 mcg was 0.152 L (95% CI: 0.066, 0.237).
In addition, the mean FEV1 results at each visit are displayed in Figure 6.
Figure 6: Mean Change from Baseline in Trough FEV1 at Each Visit by Treatment Group
Trial 2 (FAS)
FS MDPI = fluticasone propionate/salmeterol multidose dry powder inhaler: FP MDPI = fluticasone propionatemultidose dry powder inhaler; FAS = full analysis set; FEV1 = forced expiratory volume in 1 secondSupportive evidence of efficacy for fluticasone propionate/salmeterol MDPI compared withplacebo was derived from secondary endpoints such as the weekly average of daily troughmorning peak expiratory flow and total daily use of rescue medication. There were fewerwithdrawals due to worsening asthma in patients treated with fluticasone propionate/salmeterolMDPI than with placebo. The AQLQ for patients age ≥ 18 years or the PAQLQ for patients aged
12-17 were assessed in Trial 2. The responder rate for both measures was defined as animprovement in score of 0.5 or more as threshold. In Trial 2, the responder rate for patientsreceiving fluticasone propionate/salmeterol MDPI 113/14 mcg and fluticasonepropionate/salmeterol MDPI 232/14 mcg was 48% and 41%, respectively, compared to 27% forpatients receiving placebo, with an odds ratio of 2.59 (95% CI: 1.56, 4.31) and 1.94 (95% CI:1.16, 3.23), respectively.
Improvements in lung function occurred within 15 minutes of the first dose (15 minutespostdose). Compared with placebo, for fluticasone propionate/salmeterol MDPI 113/14 mcg and232/14 mcg the difference in LS mean change from baseline in FEV1 was 0.160 L and 0.187 L,respectively (unadjusted p-value <0.0001 for both doses compared with placebo). Maximumimprovement in FEV1 generally occurred within 3 hours for both fluticasonepropionate/salmeterol MDPI dose groups, and improvements were sustained over the 12 hours oftesting at weeks 1 and 12 (Figure 7 and Figure 8). Following the initial dose, predose FEV1relative to day 1 baseline improved markedly over the first week of treatment and t |
