Table 1.
Summary of the studies and data used for population pharmacokinetic and pharmacokinetic–pharmacodynamic analyses
| Study type |
Target population |
Apixaban dose and regimen | Treatment duration | Number of apixaban concentration observations (no. subjects) |
Number of anti‐FXa activity observations (no. subjects) |
|
|---|---|---|---|---|---|---|
| Phase I studiesa | ||||||
| Multiple doses16 | Healthy subjects |
2.5–25 mg b.i.d. 10–25 mg q.d. |
7 days | 1,052 (36) | 0 | |
| Single dose17 | Healthy Caucasian and Japanese subjects | 2.5, 10, 25, and 50 mg | Single dose | 1,440 (24) | 0 | |
| Age and gender15 | Healthy young and elderly male and female subjects | 20 mg single dose | Single dose | 1,121 (79) | 0 | |
| Multiple doses18 | Healthy Japanese subjects | 2.5, 5, and 10 mg b.i.d. | 7 days | 639 (18) | 492 (18) | |
| Multiple doses19 | Healthy Chinese subjects | 10 mg single dose, then 10 mg b.i.d. | Single dose, then 6 days | 356 (12) | 92 (12) | |
| Body weight20 | Healthy subjects of high, normal, and low body weight | 10 mg | Single dose | 693 (55) | 99 (55) | |
| Renal impairment14 | Healthy and renally impaired subjects | 10 mg single dose | Single dose | 523 (32) | 189 (32) | |
| Multiple doses21 | Healthy subjects | 2.5 mg b.i.d. | 4 days | 296 (14) | 272 (14) | |
| Phase II study | ||||||
| Botticelli22 | DVT treatment subjects | 5 and 10 mg b.i.d.‡ | 3 months | 456 (241) | 452 (240) | |
| Phase III studies | ||||||
| AMPLIFY1 | DVT and PE treatment subjects | 10 mg b.i.d. for 7 days followed by 5 mg b.i.d. | 6 months | 1,044 (281) | 931 (253) | |
| AMPLIFY‐EXT2 | Prevention of recurrent DVT and PE subjects | 2.5 and 5 mg b.i.d. | 12 months | 703 (178) | 612 (171) | |
| Total | 8,323 (970) | 3,139 (795) | ||||
b.i.d., twice daily; DVT, deep vein thrombosis; q.d., once daily; VTE, venous thromboembolism.
a
aThe 20 mg q.d. data (124 subjects) were not included as time since last active dose could not be unambiguously distinguished from time since last placebo dose.