TABLE 4.
PK parameters (mean, SD) measured across Parts A‐E (PK analysis set)
| Dose (mg) | Race | Sex | Fasted/fed state | n | C max (ng/ml) | AUC0‐last (h*ng/ml) | AUC0‐inf (h*ng/ml) | T max (h) | t 1/2 (h) | MRT (h) | CL/F (L/h) | V z/F (L) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A | ||||||||||||
| 80 | Asian | Male | Fasted | 1 | 151 | 419 | 436 | 5 | 2.2 | 5.3 | 183.4 | 592.4 |
| 160 | Asian | Male | Fasted | 1 | 414 | 1118 | 1261 | 5 | 6.2 | 6.8 | 126.9 | 1141.8 |
| Part B | ||||||||||||
| 240 | Asian | Male | Fasted | 6 | 295.5 (161.5) | 1262.4 (519.5) | 1324.9 (522.1) | 4.2 (1.0) | 3.6 (2.0) | 6.5 (2.6) | 199.5 (57.6) | 1029.6 (734.4) |
| 480 | Asian | Male | Fasted | 6 | 403.5 (77.4) | 2375.3 (863.0) | 2494.7 (884.3) | 3.8 (1.1) | 5.5 (4.8) | 8.2 (4.3) | 216.5 (87.8) | 1572.9 (1260.2) |
| 720 | Asian | Male | Fasted | 6 | 382.8 (127.6) | 2308.9 (690.9) | 2392.8 (683.7) | 3.9 (1.5) | 4.7 (2.0) | 7.0 (2.4) | 326.3 (108.6) | 2113.1 (670.7) |
| 1200 | Asian | Male | Fasted | 6 | 390.0 (98.9) | 2528.5 (465.1) | 2813.8 (622.2) | 3.2 (0.7) | 5.6 (1.7) | 8.8 (2.0) | 445.1 (101.8) | 3445.8 (744.8) |
| Part C | ||||||||||||
| 240 | Asian | Female | Fasted | 3 | 392.3 (29.7) | 1721.2 (631.7) | 1846.3 (750.7) | 3.4 (1.2) | 3.4 (1.2) | 5.4 (0.9) | 143.0 (48.1) | 685.2 (331.1) |
| 480 | Asian | Female | Fasted | 3 | 420.3 (172.7) | 2762.3 (1246.4) | 3050.3 (1125.0) | 4.4 (0.6) | 7.8 (4.5) | 11.0 (3.1) | 172.8 (64.4) | 2032.3 (1277.3) |
| 720 | Asian | Female | Fasted | 3 | 753.3 (299.0) | 5174.3 (2955.5) | 5337.0 (3027.9) | 3.7 (0.6) | 4.5 (0.3) | 7.3 (0.5) | 163.0 (76.2) | 1085.7 (575.2) |
| 1200 | Asian | Female | Fasted | 3 | 514.7 (133.7) | 4203.2 (2112.5) | 8572.4 (9115.6) | 3.2 (0.9) | 15.7 (20.5) | 26.4 (28.2) | 303.5 (267.9) | 2590.6 (877.8) |
| Part D | ||||||||||||
| 480 | Asian | Male | Fasted | 6 | 403.5 (77.4) | 2375.3 (863.0) | 2494.7 (884.3) | 3.8 (1.1) | 5.5 (4.8) | 8.2 (4.3) | 216.5 (87.8) | 1572.9 (1260.2) |
| 480 | Asian | Male | Fed | 6 | 460.7 (71.6) | 3823.3 (1095.5) | 3911.5 (1081.6) | 5.2 (1.7) | 4.5 (1.0) | 8.7 (1.7) | 133.8 (50.1) | 871.8 (394.0) |
| Part E | ||||||||||||
| 240 | Non‐Asian | Male | Fasted | 6 | 436.5 (110.7) | 2060.9 (569.6) | 2142.1 (578.3) | 4.5 (0.8) | 6.4 (1.4) | 7.0 (1.1) | 119.5 (33.9) | 1149.5 (516.5) |
| 480 | Non‐Asian | Male | Fasted | 6 | 454.0 (195.7) | 2153.0 (1040.1) | 2272.8 (1048.0) | 3.3 (1.2) | 3.9 (1.4) | 6.2 (0.6) | 249.2 (110.3) | 1313.4 (605.6) |
| 720 | Non‐Asian | Male | Fasted | 5 | 309.4 (126.3) | 2411.0 (853.0) | 2896.3 (611.9) | 3.0 (1.2) | 8.6 (5.0) | 12.6 (5.9) | 257.1 (51.3) | 3340.1 (2339.4) |
Abbreviations: AUC0‐inf, area under the plasma concentration–time curve from time zero to infinity; AUC0‐last, area under the plasma concentration–time curve from time zero to last measurable time point; CL/F, apparent total body clearance; C max, maximum plasma concentration; MRT, mean residence time; PK, pharmacokinetics; SD, standard deviation; t 1/2, terminal elimination half‐life; t max, time to maximum plasma concentration; V z/F, apparent volume of distribution during terminal phase.