Table 6.

Mean (plus or minus SD) PK and PD parameters in SCD patients

Dosing duration 28 d*Dosing duration ≥90 d
Voxelotor/placebo, mg/dPlacebo5007001000700900
RBC PK parameters
 Cmax, μg/mL271 ± 102329 ± 129483 ± 239242 ± 99.7336 ± 61.8
 AUC0-24, h × μg/mL5050 ± 13207560 ± 221010 100 ± 47905200 ± 23007250 ± 1430
Plasma PK parameters
 Cmax, μg/mL3.6 ± 0.85.2 ± 1.98.1 ± 2.84.9 ± 2.06.3 ± 1.9
 AUC0-24, h × μg/mL60 ± 12.995.7 ± 28.2151 ± 49.783.1 ± 38.8128 ± 27.1
PD parameters (obtained from whole blood)
 p50, mm Hg34.3 ± 3.330.9 ± 2.129.6 ± 2.628.0 ± 3.2NDND
 p20, mm Hg18.4 ± 1.615.1 ± 1.813.9 ± 3.110.0 ± 3.2NDND
 % Hb Mod, %−1.4 ± 4.410.6 ± 7.214.7 ± 9.627.0 ± 11.612.7 ± 4.419.8 ± 4.5
  • —, not applicable; AUC0-24 indicates area under the concentration-time curve from time 0 to 24 hours; Cmax, maximum blood or plasma concentration; % Hb Mod, percentage hemoglobin modification; ND, not determined; p20 and p50, partial pressure of O2 at which Hb is 20% or 50% saturated with O2; SD, standard deviation.

  • * Parameters on day 28 (at 6 hours postdose for PD).

  • Parameters on day 90 (at 6 hours postdose for PD).

  • Percentage Hb occupancy derived from voxelotor RBC concentrations at 6 hours postdose on day 90.