Table 4.
Epacadostat pharmacokinetic parameters at steady state (cycle 1/day 8) per noncompartmental analysis.
| Treatment group | N | C max, nM | t max, h | C min, nM | AUC0-t, h*nM | AUC0-τ, h*nM | t ½, h | CLss/F, L/h | |
|---|---|---|---|---|---|---|---|---|---|
| A | mFOLFOX6 | 6 | 586 ± 256 (535) |
2.9 (1-4.1) | 73.5 ± 31.2 (68.5) |
1890 ± 762 (1760) |
2790 | 1.78 | 81.7 |
| B | Nab-paclitaxel and gemcitabine |
7 | 842 ± 377 (731) |
2 (1-4) | 174 ± 183 (123) |
2890 ± 1630 (2480) |
2760 | 1.42 | 82.6 |
| C | Paclitaxel and carboplatin |
7 | 885 ± 328 (832) |
2 (1-4) | 75.1 ± 62.3 (NC) |
2450 ± 628 (2380) |
3240, 2440 | 2.62, 1.07 | 70.4, 93.5 |
| D | Pemetrexed and platinum agent |
5 | 505 ± 232 (448) |
2 (1-6.2) | 30 ± 21.3 (NC) |
1540 ± 442 (1470) |
1810 | 1.3 | 126 |
| E | Cyclophosphamide | 7 | 888 ± 459 (791) |
2 (1-6) | 98 ± 54.5 (83.1) |
2830 ± 1660 (2420) |
3410 ± 1310 (3220;n =3) |
1.84 ± 0.134 (1.84;n =3) |
75.5 ± 34.4 (70.8;n =3) |
| F | Gemcitabine and platinum agent |
7 | 980 ± 331 (925) |
2.1 (0-4) | 194 ± 206 (NC) |
3130 ± 1050 (2940) |
3770 ± 3040 (3020;n =3) |
56.4 ± 95 (7.46;n =3) |
92.1 ± 63.8 (75.6;n =3) |
| G | 5-FU and platinum agent | 8 | 752 ± 552 (588) |
3.1 (1-6) | 104 ± 108 (80.8) |
2070 ± 1220 (1760) |
2970, 2810 | 1.35, 1.30 | 76.8, 81.3 |
| Overall | 47 | 792 ± 395 (686) |
2 (0-6.2) | 111 ± 124 (NC) |
2440 ± 1220 (2150) |
3110 ± 1470 (2860;n =13) |
14.3 ± 45.6 (2.27;n =13) |
85.8 ± 32.9 (79.9;n =13) |
|
If n >2, data are mean ± standard deviation (geometric mean), except for tmax, which is reported as median (range). If n ≤ 2, individual values are listed.
5-FU, 5-fluorouracil; AUC0-t, area under the plasma drug concentration–time curve up to time “t”; AUC0-τ, area under the plasma drug concentration–time curve over the dosing interval; CLss/F, apparent total body clearance after oral administration at steady state; Cmax, maximum observed plasma concentration; Cmin, minimum (trough) steady-state plasma concentration; mFOLFOX6, oxaliplatin, leucovorin calcium (folinic acid), and 5 fluorouracil; nab, nanoparticle albumin-bound; NC, not calculable; t1/2, half-life; tmax, time to maximum concentration.