Table 2.
Statistical analysis of primary and secondary PK endpoints in Part B
| Endpoint | Na | Comparison versus alteplase cp, solution | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Adjusted | Ratio (%) | gSE | 92.83% CI | p value | gCV (%) | ||||
| gMean | gSE | Lower | Upper | ||||||
| Primary endpoints | |||||||||
| AUC0–tz (h⋅ng/mL) | 10.8 | ||||||||
| Alteplase cp | 16 | 369.21 | 1.03 | ||||||
| Alteplase mp | 16 | 377.35 | 1.03 | 102.20 | 1.04 | 94.87 | 110.10 | < 0.0001 | |
| Cmax (ng/mL) | 9.3 | ||||||||
| Alteplase cp | 16 | 738.35 | 1.02 | ||||||
| Alteplase mp | 16 | 781.24 | 1.02 | 105.81 | 1.03 | 99.18 | 112.88 | < 0.0001 | |
| Secondary endpoint | |||||||||
| AUC0–∞ (h⋅ng/mL) | 10.8 | ||||||||
| Alteplase cp | 16 | 371.85 | 1.03 | ||||||
| Alteplase mp | 16 | 379.90 | 1.03 | 102.17 | 1.04 | 94.79 | 110.12 | < 0.0001 | |
| Further PK endpointsb | |||||||||
| t1/2 initial (h) | |||||||||
| Alteplase cp | 17 | 0.0694 | – | – | – | – | – | 12.4 | |
| Alteplase mp | 17 | 0.0730 | – | – | – | – | – | 14.9 | |
| t1/2 terminal (h) | |||||||||
| Alteplase cp | 17 | 0.963 | – | – | – | – | – | 36.1 | |
| Alteplase mp | 17 | 0.907 | – | – | – | – | – | 29.4 | |
| tmax (h) | |||||||||
| Alteplase cp | 17 | 0.410 | – | – | – | – | – | 22.2 | |
| Alteplase mp | 17 | 0.386 | – | – | – | – | – | 24.7 | |
alteplase cp alteplase manufactured using current processes, alteplase mp alteplase manufactured using modified processes, AUC0–∞ area under the concentration–time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity, AUC0–tz area under the concentration–time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point, Cmax maximum measured concentration of the analyte in plasma, gCV geometric coefficient of variation, gMean geometric mean, gSE geometric standard error, PK pharmacokinetic, t1/2 half-life of the analyte in plasma, tmax time from dosing to maximum measured concentration of the analyte in plasma
aAn ANOVA model was applied to the data to test for bioequivalence that only considered subjects with valid PK parameters in both treatment periods
bDescriptive statistics of noncompartmental PK parameters