Pharmacokinetics of INCAGN01949
| Dose level | Tmax (hour) Median (min, max) | Cmax (ng/mL) Mean (SD) | AUC0–t (μg·hour/mL)* Mean (SD) | AUC0–∞ (μg·hour/mL)* Mean (SD) | Half-life (hour) Mean (SD) | CL/F (L/hour) Mean (SD) | Vz/F (liter) Mean (SD) |
| After the first dose (n=78) | |||||||
| 7 mg (n=4) | 0.64 (0.6, 4.4) | 1630 (735) | 185 (81.7) | 301 (108) | 206 (95.8) | 2.71×10−5 (1.44×10−5) | 0.0071 (0.0024) |
| 20 mg (n=4) | 2.53 (0.55, 4.5) | 5820 (324) | 904 (197) | 2290 (2460) | 313 (313) | 1.50×10−5 (7.87×10−6) | 0.0041 (0.0042) |
| 70 mg (n=21) | 4.3 (0.50, 25.2) | 22,300 (32,800) | 2370 (841) | 3180 (1060) | 198 (71.0) | 2.41×10−5 (7.19×10−6) | 0.0066 (0.0023) |
| 200 mg (n=17) | 0.63 (0.5, 4.5) | 39,200 (10,300) | 5400 (1820) | 8190 (4030) | 186 (90.5) | 3.14×10−5 (2.00×10−5) | 0.0075 (0.0039) |
| 350 mg (n=21) | 0.6 (0.0, 194) | 84,900 (76,700) | 10,000 (5600) | 18,300 (10,100) | 269 (191) | 2.40×10−5 (1.11×10−5) | 0.0077 (0.0034) |
| 700 mg* (n=7) | 0.7 (0.53, 4.2) | 207,000 (45,500) | 28,300 (7720) | 40,400 (12,000) | 197 (45.6) | 1.85×10−5 (4.80×10−6) | 0.0050 (0.00088) |
| 1400 mg (n=4) | 0.73 (0.0, 2.43) | 347,000 (130,000) | 61,600 (9130) | 102,000 (24,600) | 234 (65.4) | 1.43×10−5 (3.87×10−6) | 0.0046 (0.0046) |
| Steady state (n=15)† | |||||||
| 7 mg (n=2) | 0.78 (0.75, 0.8) | 2950 (163) | 427 (9.21) | NR | 176 (53.2) | 1.64×10−5 (3.54×10−7) | 0.0042 (0.0011) |
| 70 mg‡ (n=4) | 0.63 (0.50, 4.3) | 27,800 (8070) | 5490 (1560) | NR | 251 (80.9) | 2.51×10−5 (1.62×10−5) | 0.011 (0.0062) |
| 200 mg‡ (n=3) | 0.61 (0.55, 4.8) | 59,200 (24,500) | 10,700 (6560) | NR | 289 (101) | 1.31×10−5 (3.44×10−6) | 0.00424 (NR) |
*One patient was excluded from the pharmacokinetic summary because he/she only had pharmacokinetic sampling from 0 to 4 hours post dose.
†Patients received INCAGN01949 as an intravenous infusion on day 1 of each 14-day (±3) treatment cycle; steady state occurred around cycle 6. The dose levels of 20, 350, and 700 mg are not shown because only one patient had data available at steady state. The 1400 mg dose level is not shown because no patients were enrolled.
‡One patient was excluded since only one pharmacokinetic timepoint sample was collected.
AUC0−∞, area under the plasma concentration−time curve extrapolated to time infinity; AUC0−t, area under the concentration−time curve up to the last measurable concentration; CL/F, apparent oral dose clearance; Cmax, maximum plasma drug concentration; NR, not reported; SD, standard deviation; Tmax, time to maximum plasma drug concentration; Vz/F, apparent oral dose volume of distribution.