TABLE 3.
Summary of garadacimab pharmacokinetic plasma parameters
| Parameters | I.V. garadacimab | S.C. garadacimab | ||||||
|---|---|---|---|---|---|---|---|---|
| 0.1 mg/kg (n = 4) | 0.3 mg/kg (n = 4) | 1 mg/kg (n = 4) | 3 mg/kg (n = 4) | 10 mg/kg (n = 4) | 1 mg/kg (n = 4) | 3 mg/kg (n = 4) | 10 mg/kg (n = 4) | |
| AUC0–inf, h*µg/ml | ||||||||
| Mean (SD) | 967.1 (251.8) | 4348.4 (1263.3) | 9764.7 (1936.0) | 32,094.9 (7435.5) | 101,777.0 (24,163.9) | 6468.2 (2610.0) | 18,110.3 (7149.8) | 42,935.8 (7905.6) |
| Median (range) | 974.1 (711.8–1215.3) | 4336.4 (3145.6–5574.5) | 9774.6 (7390.2–12,119.5) | 31,613.7 (24,676.1–4476.3) | 95,751.4 (79,801.1–135,804.1) | 6023.0 (3885.1–9941.7) | 17,178.8 (11,147.3–26,936.4) | 44,660.8 (31,959.2–50,462.4) |
| AUC0–t, h*µg/ml | ||||||||
| Mean (SD) | 761.7 (217.1) | 4062.9 (1027.5) | 9483.9 (1861.6) | 31,278.8 (7166.9) | 100,100.6 (24,598.4) | 6006.8 (2245.8) | 17,133.3 (6301.9) | 40,701.4 (8776.2) |
| Median (range) | 717.145 (570.8–1041.6) | 4121.6 (3032.5–4975.9) | 9437.7 (7252.3–11,807.7) | 30,838.1 (24,174.8–39,264.3) | 93,015.5 (78,909.8–135,461.8) | 5652.0 (3799.4–8923.9) | 16,544.3 (10,871.9–24,572.5) | 42,412.3 (28,746.6–49,234.4) |
| CL, ml/h | ||||||||
| Mean (SD) | 9.8 (3.2) | 5.6 (1.0) | 7.0 (1.5) | 7.1 (1.8) | 8.6 (2.0) | – | – | – |
| Median (range) | 8.0 (8.0–13.5) | 5.8 (4.5–6.5) | 6.4 (6.0–9.1) | 7.2 (5.2–8.6) | 8.6 (6.5–10.9) | – | – | – |
| CL/F, ml/h | ||||||||
| Mean (SD) | – | – | – | – | – | 13.3 (3.4) | 14.6 (5.0) | 18.5 (4.3) |
| Median (range) | – | – | – | – | – | 12.6 (10.1–18.0) | 14.3 (8.9–20.6) | 17.6 (14.3–24.4) |
| Cmax, µg/ml | ||||||||
| Mean (SD) | 2.7 (0.4) | 11.0 (1.7) | 32.5 (6.3) | 109.6 (27.1) | 410.1 (17.5) | 9.4 (2.2) | 24.7 (8.0) | 59.0 (20.6) |
| Median (range) | 2.6 (2.4–3.4) | 10.5 (9.6–13.5) | 31.6 (26.6–40.3) | 100.6 (88.3–149.1) | 414.4 (386.3–425.4) | 9.7 (6.8–11.4) | 25.3 (16.0–32.4) | 62.6 (33.7–77.1) |
| t 1/2, h | ||||||||
| Mean (SD) | 353.0 (64.2) | 489.7 (206.0) | 408.2 (47.5) | 393.4 (12.2) | 344.0 (116.4) | 439.7 (101.6) | 437.2 (94.7) | 470.2 (104.4) |
| Median (range) | 337.8 (297.0–439.4) | 526.7 (209.0–696.2) | 407.1 (352.6–466.1) | 390.0 (383.2–410.5) | 332.0 (214.9–497.1) | 422.6 (347.2–566.6) | 412.9 (351.0–572.1) | 468.9 (353.0–589.7) |
| Median (IQR) Tmax, h | 3.5 (8.0) | 1.0 (5.0) | 1.0 (2.5) | 1.0 (0.0) | 1.0 (2.5) | 168.1 (38.4) | 133.2 (95.1) | 168.8 (23.9) |
| V z, L | ||||||||
| Mean (SD) | 4.8 (1.1) | 3.8 (1.2) | 4.0 (0.4) | 4.0 (1.1) | 4.2 (1.3) | – | – | – |
| Median (range) | 5.1 (3.6–5.8) | 4.3 (2.0–4.5) | 3.9 (3.7–4.6) | 4.1 (2.9–5.1) | 4.6 (2.3–5.4) | – | – | – |
| V z/F, L | ||||||||
| Mean (SD) | – | – | – | – | – | 8.1 (1.2) | 8.7 (1.6) | 12.9 (5.7) |
| Median (range) | – | – | – | – | – | 8.1 (6.7–9.6) | 8.6 (7.4–10.4) | 11.8 (7.3–20.8) |
Abbreviations: AUC0–inf, area under the plasma concentration–time curve extrapolated to infinity; AUC0–t, area under the plasma concentration–time curve from the time of dosing up to collection time t; CL or CL/F, total systemic clearance; Cmax, maximum plasma concentration; IQR, interquartile range; t 1/2, terminal elimination half‐life; Tmax, time to reach maximum concentration in plasma; V z or V z/F, volume of distribution during the elimination phase.