Mean (plus or minus SD) PK and PD parameters in SCD patients
| . | Dosing duration 28 d* . | Dosing duration ≥90 d† . | ||||
|---|---|---|---|---|---|---|
| Voxelotor/placebo, mg/d | Placebo | 500 | 700 | 1000 | 700 | 900 |
| RBC PK parameters | ||||||
| Cmax, μg/mL | — | 271 ± 102 | 329 ± 129 | 483 ± 239 | 242 ± 99.7 | 336 ± 61.8 |
| AUC0-24, h × μg/mL | — | 5050 ± 1320 | 7560 ± 2210 | 10 100 ± 4790 | 5200 ± 2300 | 7250 ± 1430 |
| Plasma PK parameters | ||||||
| Cmax, μg/mL | — | 3.6 ± 0.8 | 5.2 ± 1.9 | 8.1 ± 2.8 | 4.9 ± 2.0 | 6.3 ± 1.9 |
| AUC0-24, h × μg/mL | — | 60 ± 12.9 | 95.7 ± 28.2 | 151 ± 49.7 | 83.1 ± 38.8 | 128 ± 27.1 |
| PD parameters (obtained from whole blood) | ||||||
| p50, mm Hg | 34.3 ± 3.3 | 30.9 ± 2.1 | 29.6 ± 2.6 | 28.0 ± 3.2 | ND | ND |
| p20, mm Hg | 18.4 ± 1.6 | 15.1 ± 1.8 | 13.9 ± 3.1 | 10.0 ± 3.2 | ND | ND |
| % Hb Mod, % | −1.4 ± 4.4 | 10.6 ± 7.2 | 14.7 ± 9.6 | 27.0 ± 11.6 | 12.7 ± 4.4‡ | 19.8 ± 4.5‡ |
| . | Dosing duration 28 d* . | Dosing duration ≥90 d† . | ||||
|---|---|---|---|---|---|---|
| Voxelotor/placebo, mg/d | Placebo | 500 | 700 | 1000 | 700 | 900 |
| RBC PK parameters | ||||||
| Cmax, μg/mL | — | 271 ± 102 | 329 ± 129 | 483 ± 239 | 242 ± 99.7 | 336 ± 61.8 |
| AUC0-24, h × μg/mL | — | 5050 ± 1320 | 7560 ± 2210 | 10 100 ± 4790 | 5200 ± 2300 | 7250 ± 1430 |
| Plasma PK parameters | ||||||
| Cmax, μg/mL | — | 3.6 ± 0.8 | 5.2 ± 1.9 | 8.1 ± 2.8 | 4.9 ± 2.0 | 6.3 ± 1.9 |
| AUC0-24, h × μg/mL | — | 60 ± 12.9 | 95.7 ± 28.2 | 151 ± 49.7 | 83.1 ± 38.8 | 128 ± 27.1 |
| PD parameters (obtained from whole blood) | ||||||
| p50, mm Hg | 34.3 ± 3.3 | 30.9 ± 2.1 | 29.6 ± 2.6 | 28.0 ± 3.2 | ND | ND |
| p20, mm Hg | 18.4 ± 1.6 | 15.1 ± 1.8 | 13.9 ± 3.1 | 10.0 ± 3.2 | ND | ND |
| % Hb Mod, % | −1.4 ± 4.4 | 10.6 ± 7.2 | 14.7 ± 9.6 | 27.0 ± 11.6 | 12.7 ± 4.4‡ | 19.8 ± 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.