Table 2.
Summary of Apremilast Plasma Pharmacokinetic Parameters and Statistical Analysis
| Mean (CV%) | |||||||
|---|---|---|---|---|---|---|---|
| AUC0–∞, ng·h/mLa | Cmax, ng/mLa | Tmax, hb | t1/2, h | CL/F, L/ha | Vz/F, La | ||
| Mild renal impairment | Impaired, apremilast 30 mg (n = 8) | 3032.24 (20.9) | 273.52 (25.4) | 3.00 (2.0–4.0) | 8.54 (19.3) | 10.28 (20.9) | 123.24 (12.1) |
| Healthy matched, apremilast 30 mg (n = 8) | 3522.84 (20.6) | 252.00 (15.5) | 3.00 (2.0–4.1) | 8.34 (23.5) | 8.79 (17.5) | 106.77 (31.1) | |
| Ratio (90%CI)c | 85.9 (65.8–112.0) | 106.2 (84.7–133.1) | 0.0 (‐1.00 to 1.00) P > .9999 | 116.5 (89.3–151.9) | 120.4 (92.2–157.2) | ||
| Moderate renal impairment | Impaired, apremilast 30 mg (n = 8) | 3993.5 (51.7) | 197.2 (41.9) | 3.50 (0.5–8.0) | 11.12 (35.6) | 10.31 (70.2) | 144.31 (51.8) |
| Healthy matched, apremilast 30 mg (n = 8) | 2905.19 (22.2) | 215.31 (25.0) | 2.00 (1.0–6.0) | 8.51 (24.8) | 10.84 (25.2) | 129.12 (21.3) | |
| Ratio (90%CI)c | 122.1 (93.6–159.3) | 87.5 (69.8–109.7) | 1.0 (‐0.50 to 2.50) P = .25 | 81.9 (62.8–106.8) | 103.2 (79.0–134.8) | ||
| Severe renal impairment | Impaired, apremilast 30 mg (n = 8) | 6050.0 (50.5) | 384.3 (32.7) | 3.0 (1.0–6.0) | 11.994 (17.2) | 6.125 (45.9) | 104.11 (47.0) |
| Healthy matched, apremilast 30 mg (n = 7) | 2917.1 (17.5) | 271.0 (36.0) | 3.0 (2.0–4.0) | 9.476 (16.9) | 10.564 (17.8) | 143.29 (21.7) | |
| Ratio (90%CI)c | 188.5 (132.5–268.0) | 141.6 (102.9–194.8) | 0.00 (‐1.5 to 1.5) P > .9999 | 2.485d (NC) | 53.10 (37.3–75.4) | 67.35 (NC) | |
ANOVA, analysis of variance; AUC0–∞, area under the concentration‐versus‐time curve from time 0 to infinity; CI, confidence interval; CL/F, apparent total plasma clearance; Cmax, maximum observed plasma concentration; CV%, percent coefficient of variation; NC, not calculated; t½, elimination half‐life; Tmax, time to Cmax; Vz/F, apparent total volume of distribution.
The ratio of geometric means (renal impaired/healthy matched) with its 90%CI was calculated from an analysis of variance (ANOVA) model, based on the natural log‐transformed pharmacokinetic values. For the mild and moderate renal impairment study, the ANOVA model included group (mild and moderate), status (impaired and healthy), and group‐by‐status interaction as fixed effects and matched pair nested within group as a random effect. For the severe renal impairment study, the ANOVA model included status (impaired and healthy) as a fixed effect and matched pair as a random effect.
The Tmax is summarized by median (range); statistical comparison based on the Wilcoxon signed rank test and Hodges‐Lehmann estimate with its 90%CI for the median difference (renal impaired/healthy matched).
The geometric mean ratio and 90%CI of the geometric mean ratio are presented as percentages.
The t1/2 statistical comparison displays geometric mean difference (severely renal impaired/healthy matched).