Table 3.
Single dose and steady-state pharmacokinetic parameters of ipatasertib during the study
| Single dose pharmacokinetics | Stage I | Stage II | |||
|---|---|---|---|---|---|
| Ipatasertib 200 mg | Ipatasertib 400 mg | Ipatasertib 600 mg | Ipatasertib 200 mg | Ipatasertib 400 mg | |
| Cycle 0, Day 1 | Cycle 1, Day 1 | ||||
| (n = 2) | (n = 4) | (n = 8) | (n = 3) | (n = 3) | |
| Cmaxa, ng/mL | 151 (3.75) | 456 (36.6) | 953 (36.0) | 214 (49.9) | 328 (46.0) |
| Tmaxb, h | 2.53 (1.98–3.08) | 3.03 (1.02–4.07) | 2.57 (0.52–4.00) | 0.97 (0.95–3.98) | 3.97 (3.90–4.02) |
| t1/2c, h | 24.3 (23.7–24.8) | 18.8 (17.0–21.1) | 21.5 (16.2–33.9) | 7.34 (7.23–7.45) | NC |
| AUC0–24a, h ng/mL | 805 (30.7) | 4010 (38.6) | 5930 (33.1) | 1250 (36.4) | 2940 (29.6) |
| Steady-state pharmacokinetics | Stage I | Stage II | |||
|---|---|---|---|---|---|
| Ipatasertib 200 mg | Ipatasertib 400 mg | Ipatasertib 600 mg | Ipatasertib 200 mg | Ipatasertib 400 mg | |
| Cycle 1, Day 8 | Cycle 1, Day 15 | ||||
| (n = 2) | (n = 4) | (n = 7) | (n = 3) | (n = 3) | |
| Cmaxa, ng/mL | 186 (4.17) | 579 (43.1) | 973 (57.4) | 334 (31.3) | 452 (35.0) |
| Tmaxb, h | 1.46 (0.97–1.95) | 1.48 (0.93–4.00) | 1.97 (0.47–3.03) | 1.98 (1.95–2.02) | 3.97 (3.87–4.03) |
| t1/2c, h | 7.69 (7.49–7.90) | 7.20 (7.03–7.32) | 8.06 (6.50–10.30) | 8.29 (7.62–8.84) | NC |
| AUC0–24a, h ng/mL | 1210 (23.5) | 4870 (43.1) | 6510 (57.6) | 2710 (28.7) | 4970 (17.8) |
| Accumulation ratio | 1.82 (3.58) | 1.43 (9.41) | 1.38 (51.7) | 2.16 (10.0) | 1.69 (11.8) |
AUC0–24 Area under concentration–time curve from 0 to 24 h, NC not calculated
aGeometric mean (% CV)
bMedian (range)
cGeometric mean (range)