Table 3.
Summary of plasma PK parameters of ASC42 following single ascending doses (SAD) and multiple ascending doses (MAD)
| Dose (mg) | n | PK parameters, GM (GeoCV%) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| AUCτ (ng × h/mL) | Cmax (ng/mL) | Tmax (h)a | t1/2 (h) | CL/F (L/h) | RAUC | RCmax | |||
| SAD | |||||||||
| 5 | 6 | 420 (64.1) | 50.8 (122) | 3.50 (1.50–4.00) | 11 (27.7) | 11.9 (64.1) | – | – | |
| 15 | 6 | 1635 (26.9) | 363 (29.5) | 2.50 (1.50–3.00) | 8.11 (22.9) | 9.17 (26.9) | – | – | |
| 15 (fed) | 6 | 1295 (34.1) | 228 (29) | 5.00 (4.00–6.00) | 7.86 (39.7) | 11.6 (34.2) | – | – | |
| 50 | 6 | 12227 (25.7) | 2175 (19.8) | 3.50 (1.50–4.00) | 8.11 (34.6) | 4.09 (25.7) | – | – | |
| 100 | 6 | 25702 (26.0) | 3195 (32.9) | 4.00 (2.00–10.00) | 7.98 (21.1) | 3.9 (26.0) | – | – | |
| 200 | 6 | 62558 (93.6) | 11326 (46.4) | 1.75 (1.00–4.00) | 8.06 (29.3) | 3.2 (93.8) | – | – | |
| MAD | |||||||||
| 5 QD | Day 1 | 6 | 233 (74.4) | 39.6 (80) | 3.00 (2.00–4.02) | – | 21.4 (74.5) | – | – |
| Day 14 | 6 | 196 (54.1) | 35.2 (79.3) | 3.00 (0.50–4.00) | – | 25.5 (54.0) | 1.00 (42.0) | 1.02 (43.8) | |
| 15 QD | Day 1 | 6 | 1340 (57.8) | 260 (70.9) | 4.00 (3.00–10.00) | – | 11.2 ( 57.8) | – | – |
| Day 14 | 6 | 1752 (51.6) | 358 (55.5) | 3.50 (3.00–10.00) | – | 8.57 (51.6) | 1.31 (25.6) | 1.38 (21.3) | |
| 50 QD | Day 1 | 7 | 5363 (81) | 1067 (109) | 4.00 (1.50–12.00) | – | 9.32 (81) | – | – |
| Day 14 | 6 | 10970 (71.2) | 1751 (71.8) | 4.00 (2.00–6.00) | – | 4.56 (71.3) | 2.23 (58.5) | 1.74 (126) | |
SAD study including cohorts 1–5 with dose levels of 5, 15, 50, 100, and 200 mg in fasting condition, respectively, and a cross-over design of cohort 2 (15 mg) to study the food effect on ASC42 PK. MAD study including cohorts 6–8 with proposed dose levels of 5, 15, and 50 mg, respectively
SAD single ascending-dose, MAD multiple ascending dose, n number of subjects, AUC area under the concentration-time curve, AUCinf AUC from time 0 extrapolated to infinity, CL/F apparent oral clearance, Cmax maximum observed concentration, GeoCV% geometric percent coefficient of variation, GM geometric mean, PK pharmacokinetic, t1/2 terminal elimination half-life, Tmax time to maximum concentration, QD once daily, RAUC accumulation ratio for AUCτ, RCmax accumulation ratio for Cmax, Tmax time to maximum observed concentration
aTmax is represented as median and range