TABLE 7.
Statistical analysis of SPR719 dose proportionality in the MAD phasea
| Treatment day and group | Parameter | Geometric LS mean |
Slope (95% CI) | ||
|---|---|---|---|---|---|
| SPR720, 500 mg (n = 6) | SPR720, 1,000 mg (n = 6) | SPR720, 750 mg q12h (n = 6) | |||
| Day 1, fasted | Cmax (ng/ml) | 2,470 | 5,610 | NA | 1.18 (0.60–1.76) |
| Day 7, fasted | Cmax (ng/ml) | 2,420 | 5,110 | NA | 1.08 (0.50–1.65) |
| AUC0–12 (h ⋅ ng/ml) | 9,480 | 27,400 | NA | 1.53 (0.98–2.08) | |
| Day 1, fed | Cmax (ng/ml) | 1,410 | 3,500 | 4,690 | 1.42 (0.60–2.25) |
| Day 7, fed | Cmax (ng/ml) | 1,140 | 3,490 | 2,520 | 1.64 (0.72–2.55) |
| AUC0–12 (h ⋅ ng/ml) | 5,680 | 19,400 | 17,300 | 1.83 (0.70–2.97) | |
| Day 14, fed | Cmax (ng/ml) | 967 | 2,500 | NA | 1.37 (0.26–2.49) |
| AUC0–12 (h ⋅ ng/ml) | 5,040 | 13,300 | NA | 1.40 (0.23–2.57) | |
a
Results for Cmax and AUCs were obtained using a regression analysis on log-transformed values versus log-transformed dose using the power model (including an additional term for fed/fasted status for the model incorporating all cohorts for part 2). AUC0–12, area under the concentration-time curve (AUC) from time zero to 12 h postdose; C, cohort; CI, confidence interval; Cmax, maximum plasma concentration; LS mean, least-squares mean; NA, not applicable. Dosing of SPR720 in the 7-day dose groups was administered in the fasting state; dosing in the 14-day dose groups was administered without regard to meals.