Table 4.
Mean steady-state pharmacokinetic parameters for olaparib given alone (cycle 0) and combined with onalespib (cycle 1).a
| Dose | Dose | No. of | Cmin | Cmax | AUCt | CL/F | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| level | (mg) | Visit | patients | (ng/mL) | (ng/mL) | (ng h/mL) | (L/h) | ||||
| 0 | 200 | C0D7 | 3 | 1134 | (35.8) | 5793 | (12.2) | 34,481 | (28.7) | 5.80 | (28.7) |
| 0 | 200 | C1D1 | 3 | 783 | (97.2) | 5173 | (74.9) | 30,525 | (77.6) | 6.55 | (77.6) |
| 0 | 200 | C1D15 | 3 | 1350 | (195) | 6218 | (37.5) | 37,072 | (75.1) | 5.39 | (75.1) |
| 1 | 200 | C0D7 | 4 | 955 | (27.4) | 7058 | (11.0) | 36,972 | (12.4) | 5.41 | (12.4) |
| 1 | 200 | C1D1 | 4 | 1069 | (38.6) | 6155 | (18.2) | 36,004 | (19.3) | 5.55 | (19.3) |
| 1 | 200 | C1D15 | 3 | 895 | (56.3) | 6135 | (8.8) | 31,830 | (22.1) | 6.28 | (22.1) |
| 2 | 300 | C0D7 | 7b | 2189 | (51.8) | 9598 | (24.6) | 60,713 | (28.8) | 4.94 | (28.8) |
| 2 | 300 | C1D1 | 7b | 2230 | (50.5) | 9920 | (20.7) | 62,622 | (22.7) | 4.79 | (22.7) |
| 2 | 300 | C1D15 | 4 | 1891 | (56.4) | 8232 | (44.7) | 54,057 | (46.6) | 5.55 | (46.6) |
| 3 | 300 | C0D7 | 5 | 2408 | (111) | 9092 | (50.5) | 50,493 | (56.6) | 5.94 | (56.6) |
| 3 | 300 | C1D1 | 5 | 1229 | (29.9) | 8095 | (48.8) | 47,415 | (35.0) | 6.33 | (35.0) |
| 3 | 300 | C1D15 | 3 | 1326 | (34.3) | 6734 | (9.3) | 44,184 | (12.6) | 6.79 | (12.6) |
| 2a | 200 | C0D7 | 3 | 1837 | (1.6) | 7755 | (9.3) | 46,710 | (14.0) | 4.28 | (14.0) |
| 2a | 200 | C1D1 | 3 | 1579 | (41.8) | 7516 | (29.0) | 47,319 | (25.2) | 4.23 | (25.2) |
| 2a | 200 | C1D15 | 3 | 1567 | (49.7) | 8267 | (20.3) | 49,677 | (21.3) | 4.03 | (21.3) |
| 3a | 200 | C0D7 | 5 | 1380 | (106) | 7670 | (24.3) | 45,266 | (25.8) | 4.42 | (25.8) |
| 3a | 200 | C1D1 | 5 | 1507 | (25.1) | 8644 | (13.5) | 50,651 | (28.2) | 3.95 | (28.2) |
| 3a | 200 | C1D15 | 2 | 1327 | (5.0) | 7085 | (2.1) | 42,602 | (0.7) | 4.69 | (0.7) |
aData are reported as the geometric mean (geometric %CV).
bOne patient assigned to DL3 was erroneously treated with DL2 and included in the DL2 for the PK studies.