Table 2.
Geometric mean (CV% GM) PK parameters of evobrutinib
| Following single‐dose administration | |||||||
|---|---|---|---|---|---|---|---|
| Dose (mg) | N | AUC0–∞ (ng*hour/mL) | Cmax (ng/mL) | Tmax a (hour) | t1/2 (hour) | CL/F (mL/minute) | Vz/F (L) |
| 25 | 6 | 104 (53.6) | 69.9 (58.1) | 0.8 (0.5–1) | 1.80 (12.8) | 4,000 (53.6) | 621 (60.2) |
| 50 | 6 | 326 (35.7) | 234 (42.1) | 0.5 (0.3–1) | 2.06 (36.8) | 2,550 (35.7) | 455 (24.5) |
| 100 | 6 | 434 (30.3) | 309 (47.5) | 0.5 (0.3–0.5) | 2.56 (39.0) | 3,840 (30.3) | 850 (48.5) |
| 200 | 6 | 856 (27.0) | 555 (37.2) | 0.5 (0.5–1) | 2.09 (5.30) | 3,900 (27.0) | 703 (24.7) |
| 350 | 6 | 1,910 (41.7) | 846 (44.7) | 1.0 (0.3–2) | 6.81 (95.0) | 3,050 (41.7) | 1,800 (136) |
| 500 | 6 | 3,220 (25.0) | 1,510 (34.7) | 0.5 (0.5–2) | 6.63 (69.9) | 2,590 (25.0) | 1,490 (64.6) |
| On day 1 and day 14 of the multiple‐dose study | |||||||
| Day 1 | |||||||
| 25 | 9 | 123 (38.7) | 99.7 (44.5) | 0.5 (0.3–0.5) | 1.70 (19.9) | 3,390 (38.7) | 498 (32.9) |
| 75 | 9 | 325 (37.5) | 254 (46.0) | 0.5 (0.3–1) | 1.86 (15.1) | 3,850 (37.5) | 620 (48.6) |
| 200 | 9 | 1,110 (24.6) | 797 (43.9) | 0.5 (0.5–1) | 2.49 (34.7) | 3,000 (24.6) | 647 (42.3) |
| Dose (mg) | N | AUC0–24 h (ng*hour/mL) | Cmax (ng/mL) | Tmax a (hour) | t1/2 (hour) | R acc(Cmax)b | R acc(AUC0–24 h)b |
|---|---|---|---|---|---|---|---|
| Day 14 | |||||||
| 25 | 9 | 126 (46.4) | 80.4 (64.9) | 0.5 (0.3–1) | 1.59 (18.2) | 0.807 (0.59–1.11) | 1.03 (0.89–1.17) |
| 75 | 8 | 345 (44.6) | 252 (60.3) | 0.5 (0.3–1) | 2.29 (18.9) | 1.000 (0.65–1.54) | 1.03 (0.81–1.31) |
| 200 | 9 | 1,210 (34.0) | 782 (60.1) | 0.5 (0.5–1) | 3.62 (70.5) | 0.982 (0.71–1.35) | 1.09 (0.94–1.25) |
Geometric mean (CV% GM) values are rounded to 3 significant digits.
AUC0–∞,area under the plasma concentration‐time curve from time zero extrapolated to infinity; AUC0–24 h, area under the plasma concentration‐time curve from time zero to 24 hours; CL/F, apparent clearance; Cmax, maximum observed plasma concentration; CV% GM, geometric coefficient of variation; PK, pharmacokinetic; Racc(AUC0–24), accumulation ratio for AUC; Racc(Cmax), accumulation ratio for Cmax; Tmax, time to reach maximum plasma concentration; t1/2, terminal half‐life; VZ/F, apparent volume of distribution during terminal phase.
a
Median and range; rounded to 1 significant digit.
b
Geometric mean and 95% confidence interval.