GFH018 5 mg BID 14d-on/14d-off | GFH018 10 mg BID 14d-on/14d-off | GFH018 20 mg BID 14d-on/14d-off | GFH018 30 mg BID 14d-on/14d-off | GFH018 40 mg BID 14d-on/14d-off | GFH018 50 mg BID 14d-on/14d-off | GFH018 65 mg BID 14d-on/14d-off | GFH018 85 mg BID 7d-on/7d-off | GFH018 85 mg BID 14d-on/14d-off | |
---|---|---|---|---|---|---|---|---|---|
Single dose | (N = 4) | (N = 3) | (N = 4) | (N = 7) | (N = 4) | (N = 4) | (N = 6) | (N = 6) | (N = 9)a |
Cmax (ng/mL) | 215 (50.2) | 250 (72.2) | 743 (65.1) | 972 (82.7) | 1180 (24.7) | 1209 (85.4) | 2172 (16.3) | 2555 (29.9) | 3225 (35.5) |
Tmax (h) | 0.65 (0.40, 0.97) | 0.88 (0.42, 0.93) | 0.49 (0.43, 1.03) | 0.95 (0.37, 3.80) | 0.69 (0.37, 0.90) | 0.96 (0.47, 1.92) | 0.68 (0.48, 2.00) | 0.50 (0.50, 1.10) | 0.58 (0.45, 1.12) |
AUC0-12 (h*ng/mL) | 690 (51.3) | 819 (99.0) | 2551 (107.3) | 4250 (50.4) | 4147 (30.3) | 5100 (57.9) | 7028 (10.9) | 7455 (27.3) | 10074 (42.0) |
AUC0-t (h*ng/mL) | 754 (58.4) | 852 (111.3) | 2802 (123.7) | 4895 (48.2) | 4561 (35.3) | 5858 (50.2) | 7831 (17.8) | 8240 (27.9) | 11119 (45.5) |
AUC0-inf (h*ng/mL) | 769 (58.3) | 864 (110.5) | 2825 (123.9) | 4926 (47.8) | 4603 (35.2) | 5906 (49.3) | 7870 (17.9) | 8284 (28.1) | 11164 (45.4) |
t1/2 (h) | 4.42 (82.9) | 3.11 (106.3) | 4.90 (115.1) | 5.74 (37.6) | 8.60 (103.8)b | 5.93 (51.2) | 5.51 (34.3) | 7.45 (61.8) | 6.37 (41.6) |
Multiple dose | (N=3) | (N=3) | (N=3) | (N=7) | (N=3) | (N=2) | (N=6) | (N=5) | (N=7)c |
Cmax (ng/mL) | 165 (15.7) | 291 (124.9) | 676 (48.0) | 1167 (87.9) | 1599 (33.7) | 1253 (7.3) | 2303 (34.0) | 2193 (29.1) | 3034 (33.6) |
Tmax (h) | 0.88 (0.42, 0.95) | 0.92 (0.90, 1.27) | 0.93 (0.57, 1.08) | 1.10 (0.47, 2.58) | 0.88 (0.38, 1.00) | 0.75 (0.50, 1.00) | 1.88 (0.50, 2.00) | 0.50 (0.50, 1.00) | 0.50 (0.50, 2.05) |
t1/2 (h) | 2.67 (31.0) | 2.25 (26.5) | 2.55 (24.6) | 4.09 (36.8) | 2.45 (42.8) | 3.53 (3.1) | 2.59 (9.6) | 2.92 (18.3) | 3.01 (20.0)d |
Cmin (ng/mL) | 7.48 (208.2) | 15.8 (212.1) | 25.5 (137.3) | 144 (107.2) | 21.0 (2741.3) | 91.4 (72.9) | 129 (51.8) | 115 (92.5) | 164 (54.3) |
AUCtau (h*ng/mL) | 597 (61.1) | 997 (168.9) | 2056 (76.9) | 5605 (76.6) | 5144 (30.3) | 4432 (43.6) | 8189 (29.3) | 7732 (46.8) | 11353 (27.9) |
Racc | 1.02 (37.9) | 1.22 (40.3) | 1.15 (17.4) | 1.32 (39.4) | 1.18 (6.7) | 1.26 (9.2) | 1.17 (25.3) | 1.04 (32.5) | 1.18 (24.1)e |