Table 4.
Pharmacokinetic parameters in Japanese patients with solid tumors following TIW oral doses of crenigacestat on days 1 and 22a
| Day 1 (Dose 1) | Day 22 (Dose 10) | |||
|---|---|---|---|---|
| Crenigacestat 25 mg | Crenigacestat 50 mg | Crenigacestat 25 mg | Crenigacestat 50 mg | |
| Nb | 4/4 | 7/6 | 3/3 | 4/3 |
| tmax, median (range), h | 1.92 (1.00–1.93) | 1.93 (1.08–8.03) | 1.88 (0.95–1.92) | 1.94 (0.88–5.85) |
| Cmax, ng/mL | 324 (34) | 670 (39) | 429 (69) | 416 (70) |
| AUC0–48, ng*h/mL | 1480 (20) | 3080 (38) | 2070 (54) | 2090 (76) |
| AUC0-∞, ng*h/mL | 1480 (20) | 3080 (38) | – | – |
| t½, geometric mean (range), h | 3.64 (3.36–3.82) | 3.89 (2.94–4.84) | 4.19 (3.66–4.71) | 3.67 (3.40–4.14) |
Abbreviations: AUC0–48 area under the plasma drug concentration versus time curve from time 0 to 48 h, AUC0-∞ area under the plasma drug concentration versus time curve from time zero to infinity, Cmax maximum observed concentration, %CV percent coefficient of variation, N number of patients, PK pharmacokinetic; t½, elimination half-life; TIW, 3 times per week; tmax, time to reach Cmax
aData presented as geometric mean (%CV) unless otherwise indicated
bTwo N values reported. First N value is for Cmax and tmax, while the second N value is for remaining parameters that are dependent on terminal phase of PK profile. Parameters dependent on terminal phase only reported when 24-h time point result is available and when ([AUC0-∞-AUClast]/AUC0-∞)*100 ≤ 15%