Table 2 Summary of plasma pharmacokinetic variables of KH176
A. For the SAD study | |||||||||
SAD study | |||||||||
Dose | 10 mg (N = 4) | 30 mg (N = 4) | 100 mg (N = 4) | 100 mg (N = 4) | 300 mg (N = 4) | 800 mg (N = 4) | 2000 mg (N = 4) | ||
Food status | fasted | fasted | fasted | fed | fasted | fasted | fasted | ||
Cmax | (ng/mL) | Geomean | 12.9 | 56.2 | 167 | 165 | 766 | 2170 | 5990 |
CV% geomean | 21.3 | 21.0 | 27.2 | 7.40 | 53.9 | 27.9 | 20.9 | ||
tmax | (h) | Geomean | 1.25 | 1.25 | 1.00 | 2.50 | 0.992 | 1.50 | 0.750 |
CV% geomean | (0.500–1.50) | (0.500–1.50) | (0.500–2.00) | (2.00–3.00) | (0.500–3.00) | (1.00–1.50) | (0.500–3.00) | ||
AUClast | (h*ng/mL) | Geomean | 75.0 | 389 | 1310 | 1650 | 6320 | 21,000 | 61,200 |
CV% geomean | 14.8 | 8.16 | 16.7 | 1.67 | 20.2 | 27.5 | 9.07 | ||
AUC0-inf | (h*ng/mL) | Geomean | 474 | 1540 | 1970 | 7500 | 25,800 | 79,100 | |
CV% geomean | 8.39 | 13.1 | 1.04 | 19.1 | 33.9 | 8.82 | |||
t1/2 | (h) | Geomean | NA | 10.3 | 9.10 | 9.09 | 9.64 | 9.80 | 11.5 |
CV% geomean | 14.6 | 15.2 | 3.83 | 4.29 | 19.1 | 4.73 | |||
B. For the MAD study | |||||||||
MAD study | |||||||||
Dose | 100 mg b.i.d (n = 4) | 200 mg b.i.d (n = 4) | 400 mg b.i.d (n = 4) | ||||||
Day | 1 | 7 | 1 | 7 | 1 | 7 | |||
Cmax | (ng/mL) | Geomean | 184 | 353 | 313 | 748 | 1330 | 2100 | |
CV% geomean | 57.0 | 19.1 | 20.0 | 29.3 | 27.3 | 27.2 | |||
tmax* | (h) | Geomean | 1.25 | 1.00 | 1.75 | 2.00 | 1.00 | 1.50 | |
CV% geomean | (0.500–8.00) | (0.500–1.50) | (1.50–2.00) | (1.50–2.00) | (0.500–1.50) | (0.500–3.00) | |||
AUCtau | (h*ng/mL) | Geomean | 1090 | 2760 | 2250 | 5960 | 6890 | 14,900 | |
CV% geomean | 49.3 | 22.6 | 26.1 | 26.8 | 19.2 | 28.2 | |||
Racc | Geomean | 2.52 | 2.65 | 2.17 | |||||
CV% geomean | 31.2 | 2.5 | 14.4 | ||||||