TABLE 3.
GFH312 PK parameters after a single dose in part I.
| PK parameter, geomean (geoCV%) | GFH312 | GFH312 | GFH312 | GFH312 | GFH312 | GFH312 | GFH312 | GFH312 |
|---|---|---|---|---|---|---|---|---|
| 5 mg | 15 mg | 45 mg | 100 mg | 100 mg (Fed) | 200 mg | 360 mg | 500 mg | |
| (N = 6) | (N = 6) | (N = 6) | (N = 5) | (N = 6) | (N = 6) | (N = 5) | (N = 4) | |
| C max (ng/mL) | 118.1 (18.1) | 359.9 (35.3) | 334.8 (52.8) | 549.5 (38.1) | 806.9 (9.4) | 793.5 (28.2) | 1294.9 (15.5) | 1165.2 (29.9) |
| T max (h) a | 3.0 (2.0–4.0) | 2.1 (2.0–4.0) | 3.0 (2.0–4.2) | 6.0 (2.0–6.0) | 4.0 (2.0–6.0) | 4.0 (2.0–6.0) | 4.0 (1.0–4.0) | 4.0 (2.0–4.5) |
| AUC0–t (h ng/mL) | 1072.9 (16.8) | 3405.4 (35.4) | 4754.7 (40.9) | 8713.9 (62.3) | 8943.3 (51.3) | 18,525.1 (34.5) | 30,890.5 (52.4) | 29,636.0 (30.8) |
| AUC0–inf (h ng/mL) | 1144.2 (16.9) | 3452.9 (34.6) | 4956.6 (39.1) | 8879.0 (62.4) | 10,531.5 (34.9) b | 17,992.7 (27.9) c | 29,583.1 (62.2) d | 31,533.0 (28.4) |
| t 1/2 (h) | 6.2 (27.6) | 7.2 (27.0) | 13.7 (34.4) | 11.0 (16.2) | 8.8 (28.6) b | 16.1 (43.7) c | 16.4 (52.5) d | 17.6 (44.8) |
| CL/F (L/h) | 4.4 (16.9) | 4.3 (34.6) | 9.1 (39.1) | 11.3 (62.4) | 9.5 (34.9) b | 11.1 (27.9) c | 12.2 (62.2) d | 15.9 (28.4) |
| V z/F (L) | 39.0 (18.2) | 45.1 (25.5) | 179.2 (60.1) | 178.4 (52.7) | 120.4 (40.7) b | 257.7 (57.4) c | 287.1 (10.6) d | 403.0 (65.4) |
Abbreviations: AUC0–inf, area under the drug concentration‐time curve from time zero to infinity; AUC0–t , area under the drug concentration‐time curve from time zero to the last quantifiable concentration; AUC_%Extrap, percentage of AUC extrapolation for the calculation of AUC0–inf; C max, maximum concentration; CL/F, apparent clearance; geoCV%, geometric coefficient of variation; geomean, geometric mean; PK, pharmacokinetic; R 2adj, adjusted coefficient of determination for the regression of the λ z; SD, standard deviation; T max, time to maximum concentration; t 1/2, terminal half‐life; V z/F, apparent volume of distribution; λ z, elimination rate constant.
T max is reported as median (range).
n=5, λ z cannot be calculated accurately in one subject due to R 2adj less than 0.75.
n=5, λ z cannot be calculated accurately in one subject as AUC_%Extrap exceeds 20%.
n=3, λ z cannot be calculated accurately in two subjects as AUC_%Extrap exceeds 20%.