Table 4.
Summary of food-effect analyses for the adavosertib bid dosing schedules and RP2D
| Cohort | Parameter (units) | n | Fed | Fasted | Fed versus fasted |
|---|---|---|---|---|---|
| Geometric LS mean (95% CI) | Geometric LS mean (95% CI) | Geometric mean ratio (90% CI) | |||
|
bid 1 125 mg bid (5/9) |
AUC0–10 (h*nmol/L) | 5 | 1806.4 (1104.0, 2955.9) | 1658.8 (1017.1, 2705.3) | 1.089 (0.991, 1.197) |
| Cmax (nmol/L) | 6 | 276.2 (204.9, 372.3) | 256.7 (190.4, 346.1) | 1.076 (0.938, 1.234) | |
|
bid 2 150 mg bid (5/9) |
AUC0–10 (h*nmol/L) | 5 | 3177.3 (1525.3, 6618.2) | 3228.0 (1698.9, 6133.3) | 0.984 (0.661, 1.467) |
| Cmax (nmol/L) | 6 | 424.2 (273.1, 658.7) | 464.3 (303.7, 710.1) | 0.913 (0.728, 1.146) | |
|
qd 3.2 300 mg qd (5/2) |
AUC0–10 (h*nmol/L) | 3 | 5664.9 (66.0, 485942.8) | 5340.4 (65.0, 439027.6) | 1.061 (0.624, 1.802) |
| Cmax (nmol/L) | 4 | 746.6 (261.4, 2132.4) | 819.4 (305.5, 2198.0) | 0.911 (0.548, 1.514) |
AUC0–10, area under the concentration–time curve from 0 to 10 h; CI, confidence interval; Cmax, maximum concentration; LS, least-squares; n, number of patients with evaluable PK data in both fed and fasted states (PK analysis set)