Table II.
Galunisertib Noncompartmental Pharmacokinetic Parameters Following a Single Oral Dose of Galunisertib Given as Solution (Trial 1) or Either High-Sheer Wet Granulation, Roller Compaction Dry-Milled, or Roller Compaction Slurry-Milled Formulations (Trial 2)
| Parametera | Trial 1 | Trial 2 | ||
|---|---|---|---|---|
| Dose (mg) | 150 (N = 6) | 150 (N = 14) | 150 (N = 14) | 150 (N = 14) |
| Formulation | solution | HSWG | RCD | RCS |
| T max (h)b | 0.50 (0.50–0.50) | 1.00 (0.50–3.08) | 2.00 (0.50–3.17) | 2.00 (0.50–3.00) |
| C max (μ g/L) | 1480 (37) | 954 (89.7) | 734 (68.0) | 769 (67.8) |
| AUC(0-tlast) (μ g · h/L) | 3660 (36) | 4520 (58.5) | 4360 (52.0) | 4350 (63.9) |
| AUC(0-∞) (μ g · h/L) | 3670 (36) | 4740 (55.6) | 4490c (53.3) | 4790d (70.9) |
| CL/F (L/h) | 40.9 (36) | 31.7 (55.6) | 33.4c (53.3) | 31.3d (70.9) |
| Vz/F (L) | 508 (53) | 505 (88.0) | 473c (76.0) | 511d (81.9) |
| T1/2 (h) | 8.61 (4.78–19.6)b | 11.1 (47.0) | 9.81c (41.1) | 11.3d (42.4) |
AUC area under the plasma concentration versus time curve, AUC (0-∞) AUC from zero to infinity, AUC(0-t last ) AUC from time zero to time t where t is the last time point with a measurable concentration, CL/F clearance, C max maximum plasma drug concentration, CV coefficient of variation, HSWG high-sheer wet granulation, N number of subjects used in pharmacokinetic analysis, RCD roller compaction dry-milled, RCS roller compaction slurry-milled, t 1/2 half-life associated with the terminal rate constant in noncompartmental analysis, T max time of maximum plasma drug concentration, V z /F volume of distribution
aAll pharmacokinetic parameters single dose at Day 1 (geometric mean [% CV] unless stated otherwise)
bMedian (range)
c N = 12
d N = 11