Table 3.
Plasma and CSF pharmacokinetic parameters of venglustat at week 4
| Japanese (n = 9) | Non-Japanese (n = 13) | |||||
| Venglustat | Venglustat | |||||
| Low (n = 3) | Mid (n = 3) | High (n = 3) | Low (n = 4) | Mid (n = 5) | High (n = 4) | |
| Plasma pharmacokinetic parameters at week 4a | ||||||
| Cmax, ng/mL, mean (SD) | 56.3 (3.6) | 83.7 (15.1) | 145 (17.6) | 41.6 (7.4) | 77.8 (20.1) | 136 (13.4) |
| Geometric mean (CV%) | 56.2 (6.5) | 82.8 (18.0) | 144 (12.2) | 41.0 (17.8) | 75.8 (25.8) | 135 (9.9) |
| tmax, h, median (range) | 4.33 (4.33–8.00) | 2.12 (1.92–3.58) | 2.10 (1.93–3.70) | 1.96 (1.00–24.00) | 3.55 (2.00–8.03) | 2.89 (2.00–3.98) |
| AUC0–24, ng·h/mL, mean (SD) | 1130 (NA)b | 1650 (382) | 3150 (NA)c | 766 (84) | 1510 (305) | 2510 (369) |
| Geometric mean (CV%) | 1130 (NA) | 1620 (23.1) | 3140 (NA) | 763 (11.0) | 1490 (20.2) | 2490 (14.7) |
| CLSS/F, mL/h, mean (SD) | 3540 (NA)b | 5010 (1070) | 4780 (NA)c | 5270 (626) | 5450 (1010) | 6100 (1050) |
| Geometric mean (CV%) | 3540 (NA) | 4930 (21.3) | 4770 (NA) | 5240 (11.9) | 5370 (18.5) | 6030 (17.2) |
| CSF pharmacokinetic concentrations at week 4 (2–4 h post dose) | ||||||
| CSF concentration, ng/mL, mean (CV%) | 2.11 (7.8) | 4.33 (37.3) | 10.10 (9.1) | 1.85 (6.2)d | 3.15 (32.1)d | 5.96 (15.2)e |
aPlasma samples were collected at 1 h predose and 1, 2, 4, 8, and 24 h post dose. bn = 1. cn = 2. dOne participant from the low-dose group and two from the mid-dose group were not included in the CSF pharmacokinetic analysis because week 4 CSF sample was collected before dose instead of at the protocol-specified postdose time. eOne participant was not included in week 4 CSF analysis because sample was not collected. AUC0–24, area under the plasma concentration versus time curve from 0 to 24 h; Cmax, maximum observed concentration; CLSS/F, total systemic clearance at steady state; CSF, cerebrospinal fluid; CV%, coefficient of variation; NA, not applicable; tmax, time to maximum concentration.