Table 3

INCB001158 plasma PK parameters (Part 1 a—monotherapy)

ParameterINCB001158
50 mg two times per day
INCB001158
75 mg two times per day
INCB001158
100 mg two times per day
INCB001158
150 mg two times per day
Total
Cycle 1 day 1,* n evaluable878730
 Cmax, ng/mL795±2591350±3791480±4912080±632
 tmax, hours3.9 (2.0–4.1)2.0 (2.0–6.2)4.0 (2.1–6.1)6.0 (3.8–6.0)3.9 (2.0–6.2)
 AUC0–t, h⋅ng/mL8100±325013 800±486015 000±508022 700±8420
 AUC0–∞, h⋅ng/mL8860±381014 900±586017 100±644025 700±9320
 t1/2, hours5.5±1.45.3±1.05.7±0.75.7±0.95.6±1.0
 CL/F, L/h6240±16705620±18206710±28206430±19206260±2050
 Vz/F, L47 600±13 50040 800±809053 500±16 10052 000±15 50048 600±13 900
Cycle 1 day 15,† n evaluable677626
 Cmax, ng/mL1020±2931940±5442050±5323490±1050
 tmax, hours2.0 (1.9–4.0)4.1 (2.0–6.1)4.0 (2.1–5.9)2.0 (1.9–4.2)3.9 (1.9–6.1)
 AUC0–t, h⋅ng/mL8120±195015 800±544017 200±604029 300±10 100
 AUC0–tau, h⋅ng/mL8480±210017 500±6350‡19 000±5520‡31 000±10 700
 t1/2, hours5.7±1.15.3±1.2‡6.0±2.2‡7.0±1.76.1±1.6§
 CL/F, L/h6240±17004760±1780‡5700±2050‡5230±14005530±1660§
 Vz/F, L50 500±15 40036 700±16 400‡45 100±4280‡51 500±15 10047 000±14 200§
  • All data are presented as mean±SD, except for tmax, which is presented as median (range).

  • *Values shown are after single escalating doses.

  • †Values shown are after multiple escalating doses.

  • ‡n=4.

  • §n=20.

  • AUC0–∞, area under the concentration–time curve extrapolated to time of infinity; AUC0–t, area under the concentration–time curve from time 0 to the last measurable concentration; AUC0–tau, area under the concentration–time curve over the dosing interval; CL/F, apparent oral dose clearance; Cmax, maximum concentration; PK, pharmacokinetics; t1/2, terminal-phase disposition half-life; tmax, time to Cmax; Vz/F, apparent oral dose volume of distribution.