Table 3.

PK parameters and PARP inhibition following single and multiple daily dosing

Single talazoparib dose, mg
PK parameter0.025 (n = 3)0.05 (n = 3)0.1 (n = 3)0.2 (n = 3)0.4 (n = 3)0.6 (n = 6)0.9 (n = 6)1.0 (n = 5)1.1 (n = 7)
Tmax, median (min, max), h7.92 (1.95, 9.95)1.00 (0.80, 1.02)1.02 (1.00, 3.98)1.03 (1.00, 2.32)2.03 (0.75, 2.95)0.835 (0.75, 1.95)2.00 (1.02, 9.98)1.03 (0.73, 2.07)1.00 (0.73, 2.05)
Cmax, mean (SD), pg/mL60.0 (15.9)79.7 (7.50)214 (50.9)788 (369)1,830 (699)4,100 (1,400)6,100 (3,060)10,600 (4,220)13,200 (3,220)
AUC0–24, mean (SD), pg·h/mL952 (386)1,160 (166)3,160 (1,270)9,130 (3,540)13,500 (5,200)37,900 (12,900)58,200 (24,300)85,100 (29,100)91,600 (31,800)
AUC0–t, mean (SD), pg·h/mL3,600 (1,360)5,340 (1,960)16,600 (5,320)39,300 (11,700)43,700 (15,000)97,900 (30,000)160,000 (66,100)182,000 (62,400)201,000 (93,400)
AUC0-∞, mean (SD), pg·h/mL5,330 (1,840)8,320 (1,960)37,600 (6,620)92,700 (48,500)60,100 (15,900)120,000 (26,000)188,000 (85,700)200,000 (64,000)235,000 (111,000)
t1/2, mean (SD), h100 (11.9)129 (42.6)229 (158)212 (126)102 (27.2)58.6 (17.3)60.4 (10.9)52.9 (13.4)71.0 (20.6)
CL/F, mean (SD), L/h5.17 (2.10)6.27 (1.66)2.72 (0.532)2.61 (1.35)6.95 (1.71)5.19 (0.99)5.49 (2.08)5.39 (1.59)5.32 (1.64)
Vz/F, mean (SD), L756 (351)1,240 (742)839 (487)678 (217)1,050 (431)441 (143)468 (169)415 (170)549 (232)
Multiple daily talazoparib dosing, mg/day
0.025 (n = 3)0.05 (n = 2)0.1 (n = 2)0.2 (n = 3)0.4 (n = 3)0.6 (n = 6)0.9 (n = 5)1.0 (n = 6)1.1 (n = 4)
Tmax, median (min, max), h1.02 (0.58, 3.98)5.43 (0.77, 10.1)0.76 (0.75, 0.82)1.97 (1.00, 3.02)0.98 (0.75, 2.00)1.04 (0.73, 5.98)1.02 (0.97, 2.07)1.02 (0.75, 2.00)1.48 (0.98, 2.00)
Cmax, mean (SD), pg/mL300 (78.8)615 (74.2)1,880 (332)5,620 (3,530)6,560 (1,500)11,300 (3,230)15,400 (1,540)21,000 (7,990)23,400 (4,810)
AUC0-24, mean (SD), pg·h/mL3,960 (759)9,770 (2,440)30,000 (4,490)83,100 (49,300)67,300 (22,600)119,000 (19,900)157,000 (24,500)202,000 (54,000)188,000 (29,200)
t1/2, mean (SD), h107 (84.2)132 (12.3)98.2 (4.83)50.9 (19.1)90.7 (32.7)63.7 (12.7)71.0 (14.5)50.0 (16.6)52.8 (23.2)
CLss/F, mean (SD), L/h6.43 (1.23)5.28 (1.32)3.37 (0.502)3.12 (1.91)6.40 (2.07)5.15 (0.897)5.86 (0.951)5.24 (1.39)5.96 (0.837)
Vz/F, mean (SD), L1,070 (971)1,020 (345)475 (47.8)264 (249)818 (326)477 (136)604 (169)373 (144)472 (254)
Cmin, mean (SD), pg/mL169 (58.0)299 (133)1,020 (107)2,880 (1,710)2,230 (957)3,470 (1,050)3,180 (802)3,720 (1,590)2,910(803)
PARP activity, % baseline
0.025 (n = 3)0.05 (n = 3)0.1 (n = 3)0.2 (n = 3)0.4 (n = 3)0.6 (n = 4)0.9 (n = 4)1.0 (n = 4)1.1 (n = 2)
PARP activity, mean (SD)172 (206)141 (52.5)102 (98.0)14.7 (5.04)111 (96.5)24.7 (8.19)34.7 (27.4)21.1 (14.9)16.3 (5.63)
  • Abbreviations: AUC0–24, AUC from 0 to 24 h; AUC0–∞, AUC from time 0 extrapolated to infinity; AUC0–t, AUC from time 0 to last quantifiable concentration; CLss/F, CL/F at steady state; SD, standard deviation; Tmax, time to Cmax.