Table 2.
Primary and Secondary Pharmacodynamic Endpoints (Per Protocol Population)
| Change From Baseline | Placebo (n = 32)a | navafenterol 400 μg (n = 34) | navafenterol 1800 μg (n = 31) | Indacaterol 150 μg (n = 32) | Tiotropium 18 μg (n = 30) |
|---|---|---|---|---|---|
| Trough FEV1 on day 2, L (primary endpoint) | |||||
| Trough FEV1 value | −0.040 (− 0.093, 0.013) | 0.071 (0.019, 0.123) | 0.170 (0.166, 0.224) | 0.101 (0.048, 0.154) | 0.105 (0.051, 0.159) |
| Difference vs placebo | 0.111 (0.059, 0.163) | 0.210 (0.156, 0.264) | 0.141 (0.087, 0.195) | 0.145 (0.090, 0.200) | |
| P-value | < .0001 | < .0001 | < .0001 | < .0001 | |
| Difference vs indacaterol | −0.030 (−0.083, 0.023) | 0.0689 (0.015, 0.123) | |||
| P-value | .2600 | .0126 | |||
| Difference vs tiotropium | −0.034 (−0.088, 0.020) | 0.0651 (0.011, 0.120) | |||
| P-value | .2141 | .0197 | |||
| Peak FEV1 on day 1, L | |||||
| Peak FEV1 value | 0.121 (0.044, 0.198) | 0.339 (0.264, 0.413) | 0.406 (0.328, 0.483) | 0.348 (0.271, 0.424) | 0.260 (0.181, 0.340) |
| Difference vs placebo | 0.218 (0.122, 0.314) | 0.285 (0.186, 0.384) | 0.227 (0.128, 0.326) | 0.139 (0.039, 0.240) | |
| P-value | < .0001 | < .0001 | < .0001 | .0069 | |
| Difference vs indacaterol | −0.009 (−0.106, 0.088) | 0.058 (−0.041, 0.157) | |||
| P-value | .8556 | .2476 | |||
| Difference vs tiotropium | 0.079 (−0.020, 0.178) | 0.146 (0.045, 0.246) | |||
| P-value | .1180 | .0048 | |||
| Normalized AUC0–24 of FEV1, L | |||||
| Normalized FEV1 AUC0–24 value | −0.021 (−0.075, 0.032) | 0.168 (0.115, 0.221) | 0.255 (0.201, 0.309) | 0.159 (0.105, 0.212) | 0.126 (0.072, 0.180) |
| Difference vs placebo | 0.189 (0.150, 0.228) | 0.276 (0.236, 0.316) | 0.180 (0.139, 0.220) | 0.147 (0.106, 0.188) | |
| P-value | < .0001 | < .0001 | < .0001 | < .0001 | |
| Difference vs indacaterol | 0.010 (−0.030, 0.049) | 0.096 (0.056, 0.136) | |||
| P-value | .6305 | < .0001 | |||
| Difference vs tiotropium | 0.042 (0.002, 0.082) | 0.129 (0.088, 0.169) | |||
| P-value | .0406 | < .0001 | |||
| Normalized AUC0–12 of FEV1, L | |||||
| Normalized FEV1 AUC0–12 value | −0.022 (−0.081, 0.036) | 0.233 (0.175, 0.290) | 0.301 (0.242, 0.359) | 0.192 (0.134, 0.250) | 0.156 (0.096, 0.215) |
| Difference vs placebo | 0.255 (0.211, 0.299) | 0.323 (0.278, 0.368) | 0.214 (0.169, 0.260) | 0.178 (0.132, 0.224) | |
| P-value | < .0001 | < .0001 | < .0001 | < .0001 | |
| Difference vs indacaterol | 0.041 (−0.004, 0.085) | 0.109 (0.063, 0.154) | |||
| P-value | .0732 | < .0001 | |||
| Difference vs tiotropium | 0.077 (0.032, 0.123) | 0.145 (0.099, 0.191) | |||
| P-value | .0010 | < .0001 | |||
| Normalized AUC12–24 of FEV1, L | |||||
| Normalized FEV1 AUC12–24 value | −0.029 (−0.083, 0.025) | 0.104 (0.052, 0.156) | 0.212 (0.158, 0.266) | 0.128 (0.075, 0.181) | 0.100 (0.045, 0.154) |
| Difference vs placebo | 0.133 (0.085, 0.180) | 0.241 (0.192, 0.289) | 0.157 (0.108, 0.205) | 0.129 (0.079, 0.178) | |
| P-value | < .0001 | < .0001 | < .0001 | < .0001 | |
| Difference vs indacaterol | −0.024 (−0.071, 0.023) | 0.084 (0.037, 0.131) | |||
| P-value | .3172 | .0007 | |||
| Difference vs tiotropium | 0.004 (−0.044, 0.052) | 0.112 (0.064, 0.160) | |||
| P-value | .8591 | < .0001 | |||
AUC0–24 area under the curve from 0 to 24 h post-dose, AUC0–12 area under the curve from 0 to 12 h post-dose, AUC12–24 area under the curve from 12 to 24 h post-dose, FEV1 forced expiratory volume in 1 s. Values are least squares means (95% confidence interval).
aTwo patients from the placebo group were excluded from the normalized FEV1 AUC12–24 analysis due to missing data. One patient was missing data from 12 to 24 h post-dose and the other from 14 h post-dose. For all other endpoints in this table, all patients exposed to each treatment were included in the analyses