Table 4.

Pharmacokinetics

Study armDose level, mgPatient (n)Cmax, ng/mL (mean ± SD)Tmax, h (mean ± SD)Vz/F (L)Cl/F, L/hT1/2, hAUCinf (h × ng/mL ± SD)
10.530.16 ± 0.080.63 ± 0.130.35 ± 0.12
130.07 ± 0.010.93 ± 0.23
230.96 ± 0.040.82 ± 0.281.82 ± 0.31
331.36 ± 0.071.11 ± 0.193.86 ± 2.54
4.540.95 ± 0.680.83 ± 0.651.42 ± 0.63
660.97 ± 0.380.67 ± 0.211.46 ± 0.11
844.02 ± 0.751.07 ± 0.218.77 ± 4.32
1042.86 ± 0.330.94 ± 0.285.53 ± 0.30
12162.84 ± 0.570.88 ± 0.226.82 ± 0.42
1652.44 ± 1.140.95 ± 0.197.91 ± 3.72
28171.21 ± 0.181.10 ± 0.2111,180 ± 2,0783,346 ± 7303.88 ± 0.994.88 ± 1.03
1030.76 ± 0.120.89 ± 0.1114,209 ± 4,0274,574 ± 1,5272.22 ± 0.332.7 ± 0.81
FE fasta862.39 ± 1.280.94 ± 0.226.47 ± 3.15
FE fedb860.73 ± 0.171.27 ± 0.313.21 ± 0.85

NOTE: In arm 1, both interpatient and intrapatient variability (CV%) was calculated for Cmax, Tmax, and AUC parameters for all patients on all dose levels for each of the 3 pharmacokinetic sampling days. Median composite variability was calculated for all 3 days. The composite CV% for both interpatient and intrapatient variability for Cmax was 70% versus 47% and for AUC, 80% versus 45%, respectively. Tmax was similar between the 2 groups with a CV% of 40%.

Abbreviations: Arm 1, intermittent dosing; arm 2, continuous dosing; FE, food effects; SD, stable disease.

  • aPX-866 was administered while patients were fasting.

  • bPX-866 was administered with intake of food.