TABLE 8.
Summary of statistical analysis of SPR719 accumulation in MAD phasea
| SPR720 group | Parameter | Geometric LS mean |
Geometric LS mean accumulation ratio (%) (90% CI) |
|||
|---|---|---|---|---|---|---|
| Day 1 | Day 7 | Day 14 | Day 7/day 1 | Day 14/day 1 | ||
| 500 mg (n = 6) | Cmax (ng/ml) | 2,470 | 2,420 | 97.7 (73.9–129.3) | NA | |
| AUC0–24 (h ⋅ ng/ml) | 16,800 | 9,970 | 59.3 (39.4–89.2) | NA | ||
| 1,000 mg (n = 6) | Cmax (ng/ml) | 5,610 | 5,100 | 90.9 (74.4–111.1) | NA | |
| AUC0–24 (h ⋅ ng/ml) | 57,000 | 30,600 | 53.7 (37.8–76.1) | NA | ||
| 1,500 mg (750 mg q12h) (n = 6) | Cmax (ng/ml) | 4,490 | 2,520 | 56.1 (47.3–66.5) | NA | |
| AUC0–12 (h ⋅ ng/ml) | 29,200 | 17,300 | 59.2 (46.2–75.9) | NA | ||
| 500 mg (n = 6) | Cmax (ng/ml) | 1,410 | 1,140 | 967 | 80.9 (48.5–135.2) | 68.7 (38.3–123.3) |
| AUC0–24 (h ⋅ ng/ml) | 9,420 | 6,260 | 5,640 | 66.4(31.8–138.7) | 59.9 (29.6–121.0) | |
| 1,000 mg (n = 6) | Cmax (ng/ml) | 3,500 | 3,490 | 2,500 | 99.9 (61.4–162.7) | 71.6 (45.1–113.6) |
| AUC0–24 (h ⋅ ng/ml) | 35,700 | 21,600 | 14,500 | 60.4 (34.8–105.0) | 40.5 (27.2–60.4) | |
Mixed-effects ANOVA was performed on log-transformed data with the fixed effect of study day and a random effect of subjects. Parameter estimates for AUC0–24 were calculated as a partial area based on the actual predose sampling time of the following day, where a bleed time deviation occurred at the 24-h time point and the kel was not calculable. ANOVA, analysis of variance; AUC0–12, area under the concentration-time curve (AUC) from time zero to 12 h postdose; AUC0–24, AUC from time zero to 24 h postdose; CI, confidence interval; Cmax, maximum plasma concentration; LS mean, least-squares means; 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.