TABLE 2.
Descriptive summary of plasma and urine talazoparib PK parameters following multiple oral 0.5‐mg doses of talazoparib by hepatic function (day 22): PK‐evaluable analysis set
| Parameter summary statistics a by hepatic function group | ||||
|---|---|---|---|---|
| Normal hepatic function | Mild hepatic impairment | Moderate hepatic impairment | Severe hepatic impairment | |
| Plasma PK | ||||
| N, n | 6, 6 | 6, 6 b | 3, 3 | 2, 2 c |
| AUC0−24 (ng•h/mL) | 111.8 (30) | 159.0 (99) | 123.6 (30) | 243.0 (184, 302) |
| C max (ng/mL) | 10.30 (23) | 11.30 (65) | 13.56 (23) | 17.15 (11.6, 22.7) |
| T max (h) | 1.50 (0.50, 2.13) | 2.13 (1.05, 4.00) | 1.05 (1.00, 2.75) | 4.000 (2.08, 5.92) |
| CL/F (L/h) | 4.471 (30) | 3.144 (99) | 4.044 (30) | 2.187 (1.66, 2.72) |
| R ac | 5.070 (24) | 5.134 (68) | 4.771 (31) | 22.83 (22.8, 22.8) |
| Ctrough (ng/mL) d | 2.624 (28) | 3.699 (197) | 3.553 (8) | 6.225 (2.05, 10.4) |
| f u (%) e | 26.98 (23) | 27.71 (18) | 27.10 (9) | 34.72 (23.1, 45.4) |
| AUC0−24u (ng•h/mL) | 30.17 (11) | 45.08 (84) | 33.50 (35) | 64.97 (60.2, 69.8) |
| C maxu (ng/mL) | 2.778 (27) | 3.204 (56) | 3.675 (28) | 4.518 (3.79, 5.24) |
| CLu/F (L/h) | 16.57 (11) | 11.09 (84) | 14.92 (35) | 7.739 (7.17, 8.31) |
| Urine PK | ||||
| N, n | 6, 6 | 6, 5 | 3, 3 | 2, 2 |
| Ae0−24 (mg) | 0.2229 (30) | 0.1819 (34) | 0.1867 (32) | 0.1475 (0.104, 0.191) |
| Ae0−24 (%) | 44.58 (30) | 36.36 (34) | 37.40 (31) | 29.50 (20.8, 38.2) |
| CLr (L/h) | 1.993 (57) | 1.449 (92) | 1.510 (39) | 0.5986 (0.565, 0.632) |
Abbreviations: Ae0−24, amount of drug excreted in urine from time 0 to 24 hours post‐dose; AUC0−24, area under the concentration‐time curve from 0 to 24 hours; AUC0−24u, unbound AUC0−24; CL/F, apparent clearance from plasma after oral administration; CLr, renal clearance; CLu/F, unbound CL/F; Cmax , maximum observed plasma concentration; C maxu, unbound C max; C trough, predose plasma drug concentration; f u, fraction of unbound drug in plasma; N, number of PK‐evaluable patients in each group; n, number of patients contributing to summary statistics (except for R ac, C trough and f u); NA, not available as n is less than 3; PK, pharmacokinetics; R ac, accumulation ratio; T max, time to C max.
Geometric mean (geometric coefficient of variation [CV%]) for all except median (range) for T max and arithmetic mean (min, max) for group D due to n = 2;
n = 3 for C trough, n = 8 for f u and n = 5 for R ac;
n = 5 for f u and n = 1 for R ac;
For C trough to be included in this summary, the plasma sample needs to be drawn within 24 ± 2 hours of the previous dose and not more than +10 min after the drug administration on the PK collection day;
fu data from all patients including PK non‐evaluable were included in the summary.