Mean plasma PK parameters of pexidartinib in AML patients after oral administration for 1 day (C1D1) and 15 days (C1D15)
| Daily dose, mg (cohort) . | C1D1 . | C1D15 . | ||||
|---|---|---|---|---|---|---|
| Cmax, ng/mL . | AUC0-4, ng × h/mL . | AUC0-6, ng × h/mL . | Cmax, ng/mL . | AUC0-4, ng × h/mL . | AUC0-6, ng × h/mL . | |
| 800 (part 1, 1) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| G-mean | 1148 | 3300 | 5184 | 4134 | 12 340 | 20 147 |
| CV, % | 133 | 121 | 111 | 47.4 | 78.9 | 64.2 |
| 1000 (part 1, 2) | ||||||
| n | 6 | 6 | 6 | 5 | 5 | 5 |
| G-mean | 2163 | 4566 | 8008 | 7294 | 22 949 | 34 013 |
| CV, % | 44.6 | 63.8 | 48.7 | 25.7 | 31.6 | 37.2 |
| 1200 (part 1, 3) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| G-mean | 2016 | 5392 | 8171 | 4291 | 14 870 | 21 595 |
| CV, % | 92.5 | 92.2 | 93.7 | 110 | 103 | 112 |
| 1400 (part 1, 4) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 2 |
| G-mean | 2534 | 5510 | 8868 | 7593 | 25 121 | 30 857 |
| CV, % | 96.3 | 139 | 101 | 40 | 37.4 | 36.3 |
| 2000 (part 1, 5) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| G-mean | 3493 | 7159 | 12 133 | 10 633 | 37 214 | 54 464 |
| CV, % | 117 | 153 | 97.5 | 61.2 | 53.6 | 48 |
| 3000 (part 1, 6) | ||||||
| n | 6 | 6 | 6 | 5 | 5 | 4 |
| G-mean | 6132 | 16 550 | 24 986 | 12 124 | 38 834 | 58 329 |
| CV, % | 51.6 | 58.6 | 67.5 | 45.1 | 42 | 47.6 |
| 4000 (part 1, 7) | ||||||
| n | 5 | 5 | 5 | 4 | 4 | 4 |
| G-mean | 3669 | 6530 | 12 766 | 10 406 | 34 446 | 51 415 |
| CV, % | 57.6 | 166 | 101 | 45.8 | 54.3 | 47.3 |
| 5000 (part 1, 8) | ||||||
| n | 4 | 4 | 4 | 4 | 4 | 4 |
| G-mean | 4714 | 11 701 | 18 881 | 11 987 | 39 477 | 56 460 |
| CV, % | 35.8 | 27.6 | 35.6 | 35.6 | 43.2 | 44.3 |
| 3000 (part 2) | ||||||
| n | 56 | 56 | 55 | 48 | 48 | 47 |
| G-mean | 4816 | 10 910 | 18 495 | 12 794 | 43 067 | 62 451 |
| CV, % | 66 | 62.6 | 60.9 | 30.8 | 28 | 28.8 |
| Daily dose, mg (cohort) . | C1D1 . | C1D15 . | ||||
|---|---|---|---|---|---|---|
| Cmax, ng/mL . | AUC0-4, ng × h/mL . | AUC0-6, ng × h/mL . | Cmax, ng/mL . | AUC0-4, ng × h/mL . | AUC0-6, ng × h/mL . | |
| 800 (part 1, 1) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| G-mean | 1148 | 3300 | 5184 | 4134 | 12 340 | 20 147 |
| CV, % | 133 | 121 | 111 | 47.4 | 78.9 | 64.2 |
| 1000 (part 1, 2) | ||||||
| n | 6 | 6 | 6 | 5 | 5 | 5 |
| G-mean | 2163 | 4566 | 8008 | 7294 | 22 949 | 34 013 |
| CV, % | 44.6 | 63.8 | 48.7 | 25.7 | 31.6 | 37.2 |
| 1200 (part 1, 3) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| G-mean | 2016 | 5392 | 8171 | 4291 | 14 870 | 21 595 |
| CV, % | 92.5 | 92.2 | 93.7 | 110 | 103 | 112 |
| 1400 (part 1, 4) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 2 |
| G-mean | 2534 | 5510 | 8868 | 7593 | 25 121 | 30 857 |
| CV, % | 96.3 | 139 | 101 | 40 | 37.4 | 36.3 |
| 2000 (part 1, 5) | ||||||
| n | 3 | 3 | 3 | 3 | 3 | 3 |
| G-mean | 3493 | 7159 | 12 133 | 10 633 | 37 214 | 54 464 |
| CV, % | 117 | 153 | 97.5 | 61.2 | 53.6 | 48 |
| 3000 (part 1, 6) | ||||||
| n | 6 | 6 | 6 | 5 | 5 | 4 |
| G-mean | 6132 | 16 550 | 24 986 | 12 124 | 38 834 | 58 329 |
| CV, % | 51.6 | 58.6 | 67.5 | 45.1 | 42 | 47.6 |
| 4000 (part 1, 7) | ||||||
| n | 5 | 5 | 5 | 4 | 4 | 4 |
| G-mean | 3669 | 6530 | 12 766 | 10 406 | 34 446 | 51 415 |
| CV, % | 57.6 | 166 | 101 | 45.8 | 54.3 | 47.3 |
| 5000 (part 1, 8) | ||||||
| n | 4 | 4 | 4 | 4 | 4 | 4 |
| G-mean | 4714 | 11 701 | 18 881 | 11 987 | 39 477 | 56 460 |
| CV, % | 35.8 | 27.6 | 35.6 | 35.6 | 43.2 | 44.3 |
| 3000 (part 2) | ||||||
| n | 56 | 56 | 55 | 48 | 48 | 47 |
| G-mean | 4816 | 10 910 | 18 495 | 12 794 | 43 067 | 62 451 |
| CV, % | 66 | 62.6 | 60.9 | 30.8 | 28 | 28.8 |
AUC0-4, area under the curve from d 0 to d 4; AUC0-6, AUC from d 0 to d 6; Cmax, maximum serum concentration; CV, coefficient of variation; G-mean, geometric mean.