Table 2.
Statistical Analysis of Unbound Evolocumab Pharmacokinetic Parameters in Healthy Individuals and Those With Hepatic Impairment After a Single 140‐mg Subcutaneous Evolocumab Dose
| Healthy Volunteers (n = 8) | Mild Hepatic Impairment (Child‐Pugh Class A) (n = 8) | Moderate Hepatic Impairment (Child‐Pugh Class B) (n = 8) | P‐Valuea | |
|---|---|---|---|---|
| AUClast (μg · day/mL) | ||||
| Least‐squares geometric mean | 96.8 | 58.8 | 51.5 | 0.09 |
| Ratio (impaired to healthy, %) | – | 60.8 | 53.2 | |
| 90% CI of ratio (impaired to healthy, %) | – | (32.1, 115.3) | (28.1, 100.9) | |
| AUC∞ (μg · day/mL) | ||||
| Least‐squares geometric mean | 107.0 | 84.8b | 60.6 | 0.06 |
| Ratio (impaired to healthy, %) | – | 79.3 | 56.6 | |
| 90% CI of ratio (impaired to healthy, %) | – | (45.8, 137.3) | (33.3, 96.2) | |
| Cmax (μg/mL) | ||||
| Least‐squares geometric mean | 11.0 | 8.6 | 7.3 | 0.18 |
| Ratio (impaired to healthy, %) | – | 78.5 | 66.0 | |
| 90% CI of ratio (impaired to healthy, %) | – | (47.8, 129.1) | (40.1, 108.4) | |
| tmax (days) | ||||
| Median | 5.0 | 5.0 | 4.5 | |
| Range | 3.0‐7.0 | 1.0‐5.0 | 3.0‐10 | |
AUC∞, area under the concentration‐time curve from time 0 to infinity; AUClast, area under the drug concentration‐time curve from time zero to time of last quantifiable concentration; CI, confidence interval; Cmax, maximum observed drug concentration; tmax, time to reach Cmax.
a
Jonckheere‐Terpstra test.
b
AUC∞ was not estimated in 1 subject, as the rate constant, λz, associated with the terminal elimination phase could not be estimated due to limited quantifiable data.