Table 3.
Analysis of AUC and Cmax of galunisertib.
| Parameter | Formulation, 150 mg | N | Geometric LSM (90% CI) | Ratio of geometric LSM RCD/RCS:HSWG (90% CI) |
|---|---|---|---|---|
| AUC(0-tlast) (μg·h/L) | HSWG | 13 | 3,795 (3,267, 4,410) | |
| RCD | 13 | 3,704 (3,188, 4,304) | 0.98 (0.83, 1.15) | |
| RCS | 13 | 3,497 (3,009, 4,065) | 0.92 (0.78, 1.08) | |
| AUC(0–48) (μg·h/L) | HSWG | 13 | 3,797 (3,268, 4,413) | |
| RCD | 13 | 3,702 (3,186, 4,302) | 0.97 (0.83, 1.14) | |
| RCS | 13 | 3,489 (3,001, 4,056) | 0.92 (0.78, 1.08) | |
| AUC(0-∞) (μg·h/L) | HSWG | 13 | 4,026 (3,449, 4,699) | |
| RCD | 11 | 3,921 (3,328, 4,621) | 0.97 (0.84, 1.13) | |
| RCS | 10 | 3,842 (3,246, 4,547) | 0.95 (0.81, 1.12) | |
| Cmax (μg/L) | HSWG | 13 | 859 (618, 1,194) | |
| RCD | 13 | 666 (479, 925) | 0.77 (0.57, 1.06) | |
| RCS | 13 | 667 (479, 927) | 0.78 (0.57, 1.06) |
One patient (R77) who showed substantially higher exposures as explained in results was excluded from analysis. For AUC(0-∞), 2 and 3 patients for RCD and RCS, respectively had extrapolated AUC(tlast-inf) values >20% and could not be included in the analysis.
Abbreviations: AUC = area under the plasma concentration versus time curve; AUC(0-∞) = AUC from zero to infinity; AUC(0–48) = AUC from zero to 48 hours postdose; AUC(0-tlast) = AUC from time zero to time t where t is the last time point with a measurable concentration; CI = confidence interval; Cmax = maximum plasma drug concentration; HSWG = high-sheer wet granulation; LSM = least squares means; N = number of patients; PK = pharmacokinetic; RCD = roller compaction dry-milled; RCS = roller compaction slurry-milled.