Table 4.
Summary of PD parameters of FGF19 and C4 following multiple ascending doses [mean (SD)]
| FGF-19 | Time | n | AUC0‐24 h (pg × h/mL) | AUEC0‐24 h (pg × h/mL) | Emax (pg/mL) | ECFB (pg/mL) | Emax/baseline |
|---|---|---|---|---|---|---|---|
| ASC42 5 mg | Day 1 | 6 | 6714 (2709) | 1807 (1336) | 483 (221) | 278 (130) | 2.62 (0.967) |
| Day 14 | 6 | 5993 (2278) | 2985 (2054) | 527 (201) | 400 (151) | 4.71 (1.77) | |
| ASC42 15 mg | Day 1 | 6 | 7656 (1152) | 5935 (1236) | 934 (254) | 862 (257) | 13.5 (4.27) |
| Day 14 | 6 | 6155 (1984) | 5043 (1694) | 803 (279) | 757 (271) | 17.8 (4.49) | |
| ASC42 50 mg | Day 1 | 7 | 12138 (3268) | 8958 (3077) | 1369 (313) | 1236 (364) | 13.7 (8.01) |
| Day 14 | 6 | 29832 (16424) | 27054 (15590) | 3612 (1603) | 3496 (1572) | 39.7 (31.4) | |
| Pooled placebo | Day 1 | 6 | 5592 (2330) | 2157 (1906) | 499 (324) | 355 (316) | 4.37 (3.04) |
| Day 14 | 6 | 5102 (1068) | 2265 (996) | 390 (48.1) | 271 (78.7) | 5.15 (3.83) |
| C4 | Time | n | AUC0‐24 h (pg × h/mL) | AUEC0‐24 h (pg × h/mL) | Emax (pg/mL) | ECFB (pg/mL) | Emax/baseline |
|---|---|---|---|---|---|---|---|
| ASC42 5 mg | Day 1 | 6 | 168 (88.6) | − 91.1 (132) | 4.39 (2.26) | − 6.46 (6.29) | 0.48 (0.292) |
| Day 14 | 6 | 185 (118) | − 72.1 (246) | 3.53 (2.74) | − 7.32 (9.11) | 0.47 (0.437) | |
| ASC42 15 mg | Day 1 | 6 | 353 (356) | − 322 (322) | 3.38 (2.46) | − 24.8 (25.9 ) | 0.16 (0.092) |
| Day 14 | 6 | 233 (205) | − 444 (479) | 2.03 (1.78) | − 26.2 (26.6) | 0.09 (0.042) | |
| ASC42 50 mg | Day 1 | 7 | 153 (71.1) | − 361 (156) | 2.22 (0.926) | − 19.3 (7.69 ) | 0.11 (0.042) |
| Day 14 | 6 | 14.1 (16.5) | − 266 (309) | 0.83 (0.26) | − 22.8 (8.47) | 0.04 (0.034) | |
| Pooled placebo | Day 1 | 6 | 335 (174) | − 46.5 (164) | 8.69 (4.69) | − 7.27 (8.53) | 0.69 (0.249) |
| Day 14 | 6 | 410 (215) | 28.6 (300) | 8.97 (5.14) | − 6.99 (9.63) | 0.83 (0.602) |
AUC area under the concentration-time curve, AUC0–24h AUC from time 0–24 h, AUEC0–24h area under the effect curve from time 0–24 h; C4, 7-alpha-hydroxy-4-cholesten-3-one, Emax maximum effect, ECFB maximum change from baseline effect, Emin minimum effect, FGF-19 fibroblast growth factor 19, MAD multiple ascending dose, n number of subjects, SD standard deviation