Table 3.
Steady-state (day 7) PK parameters of alisertib enteric-coated tablet
| Dose (mg BID) | 20 (n = 3) |
40 (n = 3) |
50 (n = 11) |
60 (n = 2) |
|---|---|---|---|---|
| Geometric mean Cmax, nM (CV %) | 1279 (35) | 1830 (39) | 2907 (49) | 3027 |
| Geometric mean AUC, nM*hr (CV %) | 10184 (24) | 13694 (59) | 20867 (49) | 28709 |
| Median Tmax, hr (range) | 3 (1–6) | 3 (2–6) | 2.4 (0–8) | 2.8 (2.6–3) |
| Mean t1/2, hr (SD) | 16 (1.2) | 19 | 21 (10) | 28 |
| Mean peak/trough ratio (SD) | 2.1 (0.7) | 2.3 (1.4) | 2.3 (0.8) | 1.8 |
| Mean accumulation ratio (SD) | 3.0 (1.0) | 2.3 (0.4) | 2.2 (0.9) | 2.4 |
A minimum of 2 patients required to present the mean and geometric mean, and at least 3 patients required to show the standard deviation and CV; The summary statistics for 10 mg cohort is not shown as n = 1
AUC area under the curve of the dosing interval; BID twice a day; Cmax maximum concentration; CV coefficient of variation; PK pharmacokinetic; SD standard deviation; Tmax time to maximum concentration; t1/2 half life