Table 5.

Plasma ARQ 197 pharmacokinetic parameters over the 21-day dosing period of cycle 1

Dose twice a day, mgFormulationAUC(0–last)c, ng h/mLCmax, ng/mLtmax, ht½, h
Day 1Day 14/21dDay 1Day 14/21dDay 1Day 14/21dDay 1Day 14/21d
20aAm5,429 (n = 1)16,802 (n = 1)533 (n = 1)1,970 (n = 1)4.0 (n = 1)1.0 (n = 1)NANA
30aAm5,214 ± 2,494 (n = 3)7,370± 6,366 (n = 3)888 ± 195 (n = 3)1,123 ± 711 (n = 3)2.7 ± 1.2 (n = 3)1.7 ± 0.6 (n = 3)NA4.3 (n = 1)
40aAm7,724 ± 5,628 (n = 4)13,201 ± 10,634 (n = 3)1,277 ± 655 (n = 4)1,575 ± 1,006 (n = 3)4.1 ± 5.3 (n = 4)5.3 ± 5.8 (n = 3)1.7 (n = 1)NA
50aAm6,317 ± 4,877 (n = 6)8,537 ± 7,247 (n = 6)948 ± 574 (n = 6)1,281 ± 912 (n = 6)3.7 ± 4.2 (n = 6)1.5 ± 0.5 (n = 6)2.2 ± 0.5 (n = 3)3.0 ± 1.1 (n = 2)
70aAm12,588 ± 10,912 (n = 6)11,502 ± 8,353 (n = 6)2,365 ± 2,046 (n = 6)1,920 ± 993 (n = 6)3.5 ± 4.3 (n = 6)3.1 ± 4.4 (n = 6)2.1 ± 0.12 (n = 2)2.2 ± 0.3 (n = 2)
90aAm11,416 ± 5,965 (n = 5)12,668 ± 10,318 (n = 5)1,808 ± 386 (n = 5)2,340 ± 1,097 (n = 5)4.2 ± 2.5 (n = 5)1.3 ± 0.7 (n = 5)NA3.3 (n = 1)
120aAm16,915 ± 11,330 (n = 7)26,232 ± 24,610 (n = 6)2,403 ± 1,037 (n = 7)3,652 ± 2,709 (n = 6)3.3 ± 2.4 (n = 7)1.9 ± 1.2 (n = 6)1.5 (n = 1)2.6 ± 0.9 (n = 2)
120bAm10,469 ± 6,405 (n = 16)13,297 ± 11,293 (n = 14)1,812 ± 808 (n = 16)2,051 ± 1,278 (n = 14)2.7 ± 3.0 (n = 16)2.1 ± 1.2 (n = 14)2.7 ± 1.0 (n = 9)2.7 ± 0.8 (n = 6)
120bCA12,538 ± 10,156 (n = 4)24,609 ± 22,063 (n = 3)1,736 ± 1,121 (n = 4)2,758 ± 2,274 (n = 3)3.0 ± 1.2 (n = 4)3.3 ± 1.2 (n = 3)2.5 (n = 1)NA
150aAm11,503 ± 11,387 (n = 5)7,665 ± 3,806 (n = 4)1,716 ± 1,177 (n = 5)1,724 ± 976 (n = 4)2.2 ± 1.1 (n = 5)1.5 ± 0.6 (n = 7)NA2.5 ± 0.4 (n = 3)
150bAm18,325 ± 13,538 (n = 3)17,136 ± 12,858 (n = 3)2,480 ± 1,264 (n = 3)2,860 ± 1,165 (n = 3)6.0 ± 5.3 (n = 3)2.3 ± 1.5 (n = 3)NA3.6 (n = 1)
180aAm15,598 ± 12,203 (n = 3)20,523 ± 21,548 (n = 3)2,330 ± 1,050 (n = 3)2,733 ± 1,857 (n = 3)1.7 ± 0.6 (n = 3)4.0 ± 3.5 (n = 3)2.2 (n = 1)1.9 (n = 1)
360bCA15,623 ± 3,338 (n = 2)NA2,595 ± 1,025 (n = 2)NA4.5 ± 4.9 (n = 2)NANANA
360bCB8,257 ± 4,429 (n = 15)NA1,459 ± 740 (n = 15)NA3.1 ± 1.9 (n = 15)NANANA

NOTE: Data are reported as mean ± SD

Am, amorphous; AUC, area under the curve; CA, crystalline A; CB, crystalline B; NA, value is not applicable or cannot be calculated.

  • aIntermittent dosing: 2 weeks on ARQ 197, 1 week off.

  • bContinuous dosing of ARQ 197.

  • cAUC(0–last) = AUC(0–24 hr) for all doses with the following exceptions: AUC(0–last) = AUC(0–12 hr) for the 360 mg twice a day CA dose, AUC(0–last) = AUC(0–8 hr) for the 360 mg twice a day CB dose.

  • dPharmacokinetic parameters were measured on Day 14 for all doses with the following exceptions: 120 mg twice a day continuous doses (Day 21), 150 mg twice a day continuous dose (day 21).