Table 1.

PK parameters following a single ARX788 dose in monkeys, rats, and tumor-bearing mice.

SpeciesCynomolgus monkeySprague–Dawley ratBALB/c nude mice (with tumor)
Dosage (mg/kg)0.31.253.35101520302060901.675
N661261614441010101010
PK parametersMean ± SEMean ± SEMean ± SEMean ± SEMean ± SEMean ± SEMean ± SEMean ± SEMeanMeanMeanMeanMean
Tmax (hours)0.319 ± 0.1400.375 ± 0.1256.23 ± 5.980.375 ± 0.1250.719 ± 0.3200.518 ± 0.2680.250 ± 0.000.25 ± 0.000.2500.2500.2504.004.00
Cmax (μg/mL)6.62 ± 0.27832.5 ± 1.36101 ± 19.2156 ± 11.5222 ± 7.11372 ± &22.4508 ± 43.3714 ± 20.83761,060187016.571.2
Cmax/D22.1 ± 0.92726.0 ± 1.0930.6 ± 5.8331.2 ± 2.3022.3 ± 0.81724.9 ± 1.6125.4 ± 2.1723.8 ± 0.69318.817.720.79.8614.2
Tlast (hours)344 ± 48.7576 ± 0.00312 ± 0.00576 ± 0.00354 ± 18.8312 ± 0.00480 ± 0.00438 ± 42.0336336336432432
AUClast (μg*hour/mL)242 ± 11.802,390 ± 1558,940 ± 98418,500 ± 1,59028,100 ± 1,04041,500 ± 98355,000 ± 5,19092,300 ± 8,39036,70080,300107,0001,9405,900
AUClast/D807 ± 39.41,910 ± 1242,710 ± 2983,690 ± 3182,630 ± 72.72,760 ± 69.52,750 ± 2593,080 ± 2801,8301,3401,1901,1601,180
AUCinf (μg*hour/mL)250 ± 12.72,480 ± 17711,000 ± 1,15020500 ± 2,16044,900 ± 1,72069,300 ± 3,25064,300 ± 9,730123,000 ± 16,80063,60084,300109,0002,2806,880
AUCinf/D832 ± 42.41,990 ± 1423,350 ± 3504,110 ± 4324,530 ± 2134,670 ± 2273,210 ± 4864,100 ± 5603,1801,4001,2101,3701,380
Cl (mL/hour/kg)1.22 ± 0.07270.516 ± 0.03410.336 ± 0.03740.255 ± 0.02320.17 ± 0.02670.204 ± 0.01820.337 ± 0.05750.262 ± 0.04490.3140.7120.8260.7310.727
T1/2 (hours)99.9 ± 24.9134 ± 17.3135 ± 10.9170 ± 13.4255 ± 14.1252 ± 21.4149 ± 53.7219 ± 51.029072.157.2152160
MRTlast (hours)54.7 ± 5.86113 ± 7.59111 ± 2.84174 ± 7.38138 ± 6.00124 ± 1.03146 ± 14.9161 ± 19.813599.081.6149133
AUC % extrapolated2.91 ± 0.7603.54 ± 1.2518.3 ± 2.319.24 ± 1.6936.6 ± 2.6238.7 ± 2.5511.6 ± 7.0323.0 ± 5.0442.44.661.5115.014.3
Rsq0.99 ± 0.007960.984 ± 0.004990.986 ± 0.007020.996 ± 0.003690.975 ± 0.00730.971 ± 0.01020.989 ± 0.005040.939 ± 0.05490.9971.000.990.9980.991
Vss (mL/kg)81.9 ± 9.3969.1 ± 5.9959.6 ± 4.2757.9 ± 2.5359.8 ± 9.2070.1 ± 6.2065.7 ± 9.8873.1 ± 7.4812581.871.6164152
  • Note: AUClast/D and AUCinf/D units are (μg*hour/mL)/(mg/kg), and Cmax/D unit is (μg*hour/mL)/(mg/kg). Rat and mice PK analysis were performed using mean concentration profiles due to sparse PK sampling study designs.