TABLE 6.
Summary of SPR719 PK parameters following oral administration of SPR720 in healthy volunteers: MAD phase
| SPR720 treatment (n) | Day | Mean (% CV)a |
||||||
|---|---|---|---|---|---|---|---|---|
| Cmax (ng/ml) | Tmax (h) | t1/2 (h) | AUC0–12 (h ⋅ ng/ml) | AUC0–24 (h ⋅ ng/ml) | AUCinf (h ⋅ ng/ml) | Accumulation ratio | ||
| 500 mg QD, 7-day dose group (6) | 1 | 2,470 (40.8) | 4.0 (4–8) | NC | 14,700 (41.5) | 16,800 (47.2) | NC | NA |
| 7 | 2,420 (39.9) | 4 (1.5–4) | 1.67 (11.8) | 9,480 (25.8) | 9,970 (24.7) | 10,900 (19.7) | 0.593 (52.8) | |
| 1,000 mg QD, 7-day dose group (6) | 1 | 5,610 (20.1) | 4 (4–4) | NC | 43,200 (24.5) | 57,000 (34.9) | NC | NA |
| 7 | 5,110 (21.4) | 4 (1.5–4) | 2.87 (14.3) | 27,400 (34.3) | 30,600 (40.7) | 33,300 (40.2) | 0.537 (44.4) | |
| 1,500 mg total daily dose (750 mg q12h), 7-day dose group (6) | 1 | 4,690 (24.0) | 4 (4–4) | NC | 31,300 (26.0) | 54,700 (39.7) | NC | NA |
| 7 | 2,520 (34.8) | 4 (4–4) | 4.28 (70.8) | 17,300 (41.2) | 19,300 (44.0)b | 19,700 (42.1) | 0.386 (17.8) | |
| 500 mg QD, 14-day dose group (6) | 1 | 1,410 (48.5) | 4 (1–8) | NC | 8,140 (68.4) | 9,420 (75.7) | NC | NA |
| 7 | 1,140 (72.8) | 4 (1.5–8) | NC | 5,680 (97.0) | 6,260 (100.6) | NC | NC | |
| 14 | 967 (78.6) | 4 (1–8) | 5.05 (81.0) | 5,040 (93.8) | 5,640 (94.1) | 9,720 (50.8) | 0.599 (103.9) | |
| 1,000 mg QD, 14-day dose group (6) | 1 | 3,500 (28.6) | 4 (4–8) | NC | 27,500 (30.6) | 35,700 (25.8) | NC | NA |
| 7 | 3,490 (56.0) | 4 (4-4) | NC | 19,400 (63.6) | 21,600 (68.7) | NC | NC | |
| 14 | 2,500 (51.6) | 4 (4–8) | 3.67 (53.0) | 13,300 (42.5) | 14,500 (43.1) | 19,900 (24.9) | 0.405 (67.3) | |
Cmax and AUC are expressed as geometric means, Tmax values are expressed as medians (ranges), and half-life values are expressed as arithmetic means. AUC0–12, area under the concentration-time curve from time zero to 12 h; AUC0–24, area under the concentration-time curve from time zero to 24 h; AUCinf, area under the concentration-time curve from time zero to infinity; Cmax, maximum concentration; t1/2, elimination half-life; Tmax, time of maximum observed concentration; NC, not calculable. 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.
The AUC0–24 cannot be compared between day 1 and day 7 for cohort 3 (750 mg BID) since the subjects received two doses (750 mg q12 h = 1,500 mg) on day 1 but only one dose (750 mg once in the morning) on day 7.