TABLE 3.
Plasma PK parameters of SAR443820 (PK population).
| Parameter | SAD (part 1a) | PK‐CSF (part 1b) | ||||
|---|---|---|---|---|---|---|
| SAR443820 | SAR443820 | |||||
| 10 mg (n = 6) | 20 mg (n = 6) | 30 mg (n = 6) | 40 mg (n = 6) | 10 mg (n = 6) | 40 mg (n = 6) | |
| C max (ng/mL), geometric mean (%CV) | 116 (27.2) | 241 (20.5) | 417 (34.2) | 555 (28.7) | 111 (31.0) | 374 (22.0) |
| T max (h), median (range) | 1.02 (1.00, 3.08) | 1.50 (1.00, 3.00) | 1.00 (0.50, 2.00) | 1.50 (1.00, 2.00) | 4.24 (3.00, 6.00) | 4.50 (2.00, 6.00) |
| AUClast (h*ng/mL), geometric mean (%CV) | 1120 (40.1) | 2360 (19.1) | 2420 (30.2) | 5120 (34.5) | 1170 (36.6) | 3960 (30.7) |
| AUC (h*ng/mL), geometric mean (%CV) | 1170 (40.9) | 2410 (19.0) | 2440 (30.2) | 5180 (34.6) | 1370 (42.6) | 4740 (42.5) |
| T 1/2z (h), geometric mean (%CV) | 7.97 (29.0) | 7.48 (21.4) | 5.70 (31.8) | 6.29 (20.6) | 7.97 (19.4) | 8.03 (29.5) |
| Vz/F (L), geometric mean (%CV) | 98.4 (20.2) | 89.4 (14.2) | 101 (12.1) | 70.1 (23.7) | 83.6 (25.6) | 97.7 (14.3) |
| CL/F (L/h), geometric mean (%CV) | 8.56 (37.8) | 8.28 (21.4) | 12.3 (44.7) | 7.72 (36.1) | 7.27 (29.7) | 8.43 (34.2) |
| MAD (Part 2) | ||||
|---|---|---|---|---|
| SAR443820 a | ||||
| 10 mg q.d. | 20 mg q.d. | 15 mg b.i.d. | 20 mg b.i.d. | |
| Day 1 | n = 8 | n = 8 | n = 8 | n = 8 |
| C max (ng/mL), geometric mean (%CV) | 157 (20.7) | 240 (20.2) | 211 (44.2) | 205 (20.3) |
| T max (h), median (range) | 1.00 (0.50, 2.00) | 1.5 (1.00, 2.00) | 1.00 (0.50, 2.00) | 2.00 (1.00, 4.00) |
| AUCtau (h*ng/mL), geometric mean (%CV) | 1080 (24.2) | 1860 (22.5) | 1100 (33.1) | 1350 (18.4) |
| Day 14 | n = 7 | n = 8 | n = 8 | n = 7 |
| C max (ng/mL), geometric mean (%CV) | 158 (31.9) | 250 (22.7) | 268 (36.3) | 353 (19.9) |
| T max (h), median (range) | 1.00 (1.00, 2.00) | 2.00 (0.60, 2.00) | 1.00 (1.00, 2.00) | 1.00 (0.50, 2.00) |
| AUCtau (h*ng/mL), geometric mean (%CV) | 1410 (27.4) | 2130 (21.4) | 1640 (32.5) | 2160 (25.9) |
| T 1/2z (h), geometric mean (%CV) | 8.87 (23.2) | 8.53 (19.0) | 7.21 (15.6) | 7.37 (23.0) |
| CLss/F (L/h), geometric mean (%CV) | 7.08 (25.9) | 9.40 (22.2) | 9.16 (30.0) | 9.27 (24.9) |
Abbreviations: AUClast, area under the plasma concentration versus time curve from time zero to the real time t last; b.i.d., twice daily; CL/F, apparent total body clearance of a drug from the plasma after single dose; CLss/F, apparent total body clearance of a drug from the plasma at steady‐state; C max, maximum plasma concentration; CSF, cerebrospinal fluid; CV, coefficient of variation; MAD, multiple ascending dose; PK, pharmacokinetic; q.d., once daily; SAD, single ascending dose; T last, time corresponding to the last concentration above the limit of quantification, C last; T max, time to reach C max; T 1/2z, terminal half‐life; Vz/F, apparent volume of distribution during the terminal phase.
The dosing interval tau is 12 h for the b.i.d. cohorts and 24 h for the q.d. cohorts.