TABLE 3.
SAD PK parameters a
| Panel 1 milvexian 4 mg fasted (n = 6) | Panel 2 milvexian 20 mg fasted (n = 6) | Panel 3 milvexian 60 mg fasted (n = 6) | Panel 4 milvexian 200 mg fasted (n = 6) | Panel 4 milvexian 200 mg fed (n = 6) | Panel 5 milvexian 300 mg fasted (n = 6) | Panel 6 milvexian 500 mg fasted (n = 6) | Panel 6 milvexian 500 mg fed (n = 6) | Dose proportionality, slope (90% CI)b | |
|---|---|---|---|---|---|---|---|---|---|
| Cmax, ng/ml | 13.3 (68.6) | 126 (36.7) | 337 (23.6) | 1068 (98.6) | 1639 (20.9) | 1017 (34.1) | 1853 (32.0) | 3359 (39.6) | 0.9886 (0.8990, 1.0783) |
| AUC(0‐T), ng·h/ml | 125 (67.7) | 1220 (20.3) | 3793 (13.7) | 12,471 (68.0) | 17,811 (19.4) | 14,588 (29.9) | 20,991 (26.8) | 44,330 (25.0) | 1.0536 (0.9777, 1.1295) |
| AUC(INF), ng·h/ml | 210 (22.7)c | 1284 (20.2) | 4104 (11.9) | 13,759 (61.8) | 19,106 (22.0) | 15,041 (29.1) | 21,326 (26.7) | 44,796 (25.3) | 0.9491 (0.8811, 1.0170) |
| T1/2, h | 10.3 (25.7) | 8.3 (17.0) | 9.9 (13.7) | 10.5 (28.8) | 9.0 (16.1) | 13.8 (21.0) | 12.2 (14.4) | 10.7 (12.1) | N/A |
| Tmax, h | 3.00 (2.00–4.00) | 3.00 (1.00–4.00) | 3.00 (2.00–4.00) | 3.00 (2.00–4.00) | 4.00 (3.00–6.00) | 3.00 (2.00–4.00) | 3.00 (2.00–4.00) | 4.00 (4.00–6.00) | N/A |
Abbreviations: AUC, area under the plasma concentration‐time curve; AUC(0‐T), area under the plasma concentration‐time curve from time zero to the time of last quantifiable concentration; AUC(INF), area under the plasma concentration‐time curve from time 0 extrapolated to infinity; CI, confidence interval; Cmax, maximum observed plasma concentration; CV%, coefficient of variation; max, maximum; min, minimum; N/A, not applicable; PK, pharmacokinetic; SAD, single ascending dose; T1/2, terminal phase half‐life; Tmax, time of maximum observed plasma concentration.
The table provides descriptive statistics of milvexian PK parameters. Values are geometric mean (geometric CV%) for Cmax and AUCs, arithmetic means (CV%) for T1/2, and median (min‐max) for Tmax.
Dose proportionality was assessed by estimating the slope of the linear regression of Log(Cmax), Log(AUC[0‐T]), and Log(AUC[INF]) on Log(dose) using the data from panels 1 to 6 under fasted conditions.
n = 3.