TABLE 2.
Pharmacokinetic parameters following a single or multiple doses of branebrutinib
| SAD part (day 1) | MAD part (day 14) | JMAD part (day 14) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose (mg) | 0.3 (n = 6) | 1 (n = 6) | 3 (n = 6) | 10 (n = 6) | 30 (n = 6) | 0.3 | 1 | 3 | 10 | 0.3 | 3 | 10 |
| GM C max (ng mL −1 ) | 1.7 | 4.6 | 14.2 | 66.6 | 179 | 2.2 (n = 6) | 5.9 (n = 6) | 17.8 (n = 6) | 60.5 (n = 5) | 2.0 (n = 6) | 16.3 (n = 6) | 97.2 (n = 6) |
| Median T max (hr) | 0.5 | 0.5 | 0.8 | 0.5 | 0.5 | 1 (n = 6) | 0.5 (n = 6) | 0.5 (n = 6) | 0.5 (n = 5) | 0.5 (n = 6) | 0.5 (n = 6) | 0.5 (n = 6) |
| GM AUC inf (ng hr mL −1 ) | 2.4 | 8.1 | 24.5 | 100 | 282 | 3.7 (n = 5) | 10.5 (n = 6) | 30.6 (n = 6) | 101.0 (n = 5) | 3.2 (n = 5) | 27.4 (n = 6) | 139.0 (n = 6) |
| Mean t 1/2 (hr) | 1.22 | 1.59 | 1.73 | 1.56 | 1.63 | 1.30 (n = 5) | 1.66 (n = 6) | 1.64 (n = 6) | 1.74 (n = 5) | 0.91 (n = 5) | 1.51 (n = 6) | 1.70 (n = 6) |
| GM CLT/F (L/hr) | 126 | 124 | 122 | 99.6 | 106 | 81.3 (n = 5) | 95.5 (n = 6) | 98.1 (n = 6) | 99.5 (n = 5) | 94.0 (n = 5) | 109 (n = 6) | 72.2 (n = 6) |
| GM Vz/F (L) | 216 | 255 | 304 | 221 | 245 | NA | NA | NA | NA | NA | NA | NA |
AUC: area under the curve; AUCinf: AUC to time infinity; AUCtau: AUC to the end of the dosing period; CLT/F: apparent total body clearance; Cmax: maximum serum concentration; GM: geometric mean; JMAD: MAD in first‐generation Japanese participants; MAD: multiple‐ascending dose; NA: not available; SAD: single‐ascending dose; Tmax: time to reach maximum concentration; Vz/F: apparent volume of distribution at terminal phase