Table 4.
Pharmacokinetic index values for entinostat and exemestane
| (A) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Compound | Day | Dose | Cohort | Cmax | tmax | AUCinf | t1/2 | CL/F |
| (mg) | N | (ng/mL) | (h) | (h·ng/mL) | (h) | L/h | ||
| Entinostat | 1 | 3 | 3* | 49.2 ± 8.38 | 0.50 (0.25, 0.53) | 572 ± 122 | 38.3 (14.3, 218) | 5.42 ± 1.26 |
| 5 | 12 | 101 ± 62.1 | 0.50 (0.25, 7.92) | 1070 ± 364 | 51.7 (33.8, 156) | 5.08 ± 1.31 | ||
| 7 | 3 | 154 ± 39.2 | 0.55 (0.50, 1.0) | 1380 ± 206 | 48.1 (42.5, 87.6) | 5.15 ± 0.76 |
| (B) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Compound | Day | Dose | Cohort | Cmax | tmax | AUCinf | t1/2 | CL/F | AR |
| (mg) | N | (ng/mL) | (h) | (h·ng/mL) | (h) | L/h | / | ||
| Entinostat | 22 | 3 | 3* | 55.7 ± 38.2 | 0.47 (0.28, 7.92) | 609 ± 44.3 | 65.3 (61.2, 66.7) | 4.94 ± 0.36 | 1.30 ± 0.19 |
| 5 | 12 | 107 ± 63.2 | 0.50 (0.25, 8.00) | 1310 ± 349 | 61.9 (40.2, 195) | 4.00 ± 0.85 | 1.46 ± 0.19 | ||
| 7 | 3 | 122 ± 76.1 | 0.50 (0.23, 2.00) | 1650 ± 452 | 56.2 (53.6, 127) | 4.45 ± 1.14 | 1.38 ± 0.12 |
| (C) | ||||||
|---|---|---|---|---|---|---|
| Compound | Stage | Cohort | t1/2 | tmax | Cmax | AUC0–t |
| mg/dose | N | (h) | (h) | (ng/mL) | (h∙ng/mL) | |
| Exemestane | Lead in 25 mg | 21 | 6.24 (1.87, 14.0) | 1.02 (0.50, 8.03) | 17.0 (5.66, 70.5) | 54.6 (27.5, 128) |
| Combo 25 mg | 21 | 5.68 (2.22, 7.98) | 3.95 (1.95, 12.00) | 13.0 (5.06, 57.4) | 58.8 (27.1, 109) |
AUC area under the plasma concentration-time curve, CL/F oral clearance, Cmax maximum plasma concentration, t1/2 half-life
tmax and t1/2 are shown as median (Min., Max.), and other parameters are shown as mean ± SD
COVANCE-EOC103 China Ph I PK report;
*1 subject with an AUC extrapolated percentage > 30%
The data are included in the descriptive statistics