TABLE 3.
Geometric mean (mean, percentage coefficient of variation) pharmacokinetic parameters of cedirogant after multiple‐ascending doses in healthy participants (Study 2A) and patients with moderate to severe chronic plaque psoriasis (Study 2B) under fed conditions.
| Study 2A | Study 2B | ||||
|---|---|---|---|---|---|
| PK parameters (units) | Group 1: 75 mg q.d. | Group 2: 225 mg q.d. | Group 3: 375 mg q.d. | 375 mg q.d. | |
| Day 1 | Day 1 | ||||
| N | 9 | 9 | 9 | 13 | |
| C max | (μg/mL) | 1.94 (2.02, 30) | 5.96 (6.10, 23) | 9.92 (9.98, 12) | 10.7 (11.0, 25) |
| T max a | (h) | 5.0 (3.0–9.0) | 4.0 (4.0–6.0) | 4.0 (4.0–9.0) | 2.0 (1.0–6.0) |
| AUC0‐24 | (μg•h/mL) | 27.4 (28.5, 30) | 72.8 (74.8, 26) | 139 (141, 17) | 150 (154, 24) |
| C max/dose | (μg/mL/mg) | 0.0259 (0.0269, 30) | 0.0265 (0.0271, 23) | 0.0265 (0.0266, 12) | 0.0285 (0.0293, 25) |
| AUC0‐24/dose | (μg•h/mL/mg) | 0.365 (0.380, 30) | 0.324 (0.333, 26) | 0.370 (0.375, 17) | 0.400 (0.411, 24) |
| Day 7 | |||||
| N | 9 | 9 | 9 | ||
| C max | (μg/mL) | 3.30 (3.49, 36) | 7.56 (7.69, 19) | 12.3 (12.5, 17) | |
| T max a | (h) | 5.0 (3.0–9.0) | 4.0 (3.0–9.0) | 4.0 (4.0–9.0) | |
| AUC0‐24 | (μg•h/mL) | 51.7 (54.7, 37) | 104 (107, 24) | 185 (191, 26) | |
| C trough | (μg/mL) | 1.53 (1.66, 43) | 2.70 (2.87, 39) | 5.16 (5.42, 34) | |
| C max/dose | (μg/mL/mg) | 0.0440 (0.0465, 36) | 0.0336 (0.0342, 19) | 0.0328 (0.0333, 17) | |
| AUC0‐24/dose | (μg•h/mL/mg) | 0.689 (0.730, 37) | 0.463 (0.476, 24) | 0.494 (0.509, 26) | |
| C trough/dose | (μg/mL/mg) | 0.0205 (0.0221, 43) | 0.0120 (0.0128, 39) | 0.0138 (0.0144, 34) | |
| Day 14 | Day 28 | ||||
| N | 9 | 9 | 9 | 11 | |
| C max | (μg/mL) | 3.45 (3.60, 31) | 7.99 (8.19, 22) | 10.4 (10.8, 29) | 13.8 (14.2, 25) |
| T max a | (h) | 5.0 (4.0–9.0) | 4.0 (4.0–5.0) | 5.0 (3.0–9.0) | 2.0 (1.0–5.0) |
| AUC0‐24 | (μg•h/mL) | 50.9 (53.2, 32) | 101 (104, 24) | 159 (165, 27) | 206 (213, 25) |
| C trough | (μg/mL) | 1.53 (1.63, 38) | 2.57 (2.71, 32) | 4.88 (5.19, 44) | 4.50 (4.63, 26) |
| CL/F | (L/h) | 1.47 (1.54, 30) | 2.23 (2.30, 28) | 2.36 (2.46, 34) | 1.82 (1.88, 27) |
| t 1/2 b | (h) | 26.2 (7.08) | 27.1 (8.85) | 27.5 (7.39) | – |
| C max/dose | (μg/mL/mg) | 0.0461 (0.0480, 31) | 0.0355 (0.0364, 22) | 0.0277 (0.0289, 29) | 0.0367 (0.0377, 25) |
| AUC0‐24/dose | (μg•h/mL/mg) | 0.679 (0.710, 32) | 0.448 (0.460, 24) | 0.425 (0.441, 27) | 0.550 (0.567, 25) |
| C trough/dose | (μg/mL/mg) | 0.0204 (0.0218, 38) | 0.0114 (0.0120, 32) | 0.0130 (0.0138, 44) | – |
| R ac C max | (ratio) | 1.80 (1.44–2.48) c | 1.37 (1.05–1.60) c | 1.09 (0.684–1.47) c | 1.24 (0.830–2.14) e |
| R acAUC0‐24 | (ratio) | 1.84 (1.54–2.43) d | 1.38 (1.17–1.67) d | 1.20 (0.806–1.33) d | 1.26 (0.934–2.09) f |
Note: Limited data collection for Study 2B prevented t 1/2 calculations.
Abbreviations: AUC0‐24, area under the plasma concentration–time curve from time 0 to 24 h; Cl/F, apparent oral clearance; C max, maximum plasma concentration; C trough, observed plasma concentration at the end of the dosing interval; N, number of participants; PK, pharmacokinetic; q.d., once‐daily; T max, time to reach C max; t 1/2, half‐life.
Median (minimum through maximum).
Harmonic mean (pseudo‐standard deviation).
Accumulation ratio calculated as the ratio of C max on study Day 14 to C max on study Day 1, median (minimum through maximum).
Accumulation ratio calculated as the ratio of AUC0‐24 on study Day 14 to AUC0‐24 on study Day 1, median (minimum through maximum).
N = 10; accumulation ratio calculated as the ratio of C max on study Day 28 to C max on study Day 1, median (minimum through maximum).
N = 10; accumulation ratio calculated as the ratio of AUC0‐24 on study Day 28 to AUC0‐24 on study Day 1, median (minimum through maximum).