Pharmacokinetics and pharmacodynamics
Mean plasma concentrations of luvadaxistat were higher for subjects treated with 500 mg than with 50 mg doses. No accumulation was observed for subjects receiving multiple doses of luvadaxistat 50 mg (mean plasma concentration [standard deviation (SD)] of 253.4 [199.3] ng/mL on day 1 [0.25 to 2.00 h] compared with 203.5 [199.6] ng/mL on day 7 [0.25 to 2.00 h]), and trough concentrations were low at day 7 (8.749 [19.212] ng/mL) and day 8 (3.366 [2.726] ng/mL). Some accumulation of luvadaxistat was observed in subjects treated with multiple daily doses of luvadaxistat 500 mg (mean plasma concentration [SD] of 700.4 [783.0] ng/mL on day 1 [0.25 to 2.00 h] compared with 1184 [482] ng/mL on day 7 [0.25 to 2.00 h]), and trough concentrations were higher than those observed following luvadaxistat 50 mg treatment (day 7: 78.92 [229.90] ng/mL; day 8: 21.61 [14.65] ng/mL).Plasma D-serine levels increased following treatment with luvadaxistat 50 mg (range: 16.5% to 32.4%) and 500 mg (range: 11.3% to 36.4%). These levels were higher than those following placebo treatment (range: 3.2% to 7.8%). The MMRM analysis confirmed that D-serine levels following luvadaxistat treatment were significantly higher at post-baseline time points than those following placebo treatment (