Table 4.
Summary of PD Parameters of FGF19 Following Single and Multiple Ascending Doses
n | AUC0‐24 h (pg • h/mL) | Cmax (pg/mL) | Maximum Change From Baseline (pg/mL) | Difference vs Placebo (pg/mL) | ||
---|---|---|---|---|---|---|
SAD | Median (Range) Mean (SD) | Median (95%CI) | ||||
Dose (µg) | 6‐h After Dose | |||||
10 | 5 |
1250 (1040‐1410) 1230 (138) |
438 (337‐773) 489 (168) |
265 (156‐665) 313 (205) |
196.5 (−0.7 to 384.0) | |
30 | 6 |
980 (733‐2450) 1260 (662) |
416 (267‐1520) 609 (479) |
312 (168‐1330) 484 (438) |
235.4 (60.4‐676.0) | |
100 | 6 |
1450 (1020‐2130) 1540 (498) |
673 (325‐991) 704 (252) |
607 (291‐795) 578 (213) |
534.6 (320.0‐790.0) | |
300 | 6 |
2460 (782‐4900) 2660 (1500) |
1440 (447‐1730) 1210 (535) |
1250 (353‐1470) 1060 (485) |
1120.0 (405.2‐1463.0) | |
300 (fed) | 4 |
3090 (1720‐5690) 3400 (1910) |
1140 (769‐2380) 1350 (726) |
976 (567‐2200) 1180 (728) |
||
1000 | 6 |
3410 (1730‐4440) 3220 (985) |
1820 (1030‐2570) 1820 (630) |
1700 (963‐2430) 1680 (597) |
1679.0 (1058.0‐2244.0) | |
3000 | 6 |
4240 (2530‐6800) 4470 (1750) |
1750 (1400‐3250) 2070 (752) |
1570 (1260‐2950) 1860 (682) |
1554.0 (1290.3‐2563.0) |
MAD | Median (Range) Mean (SD) | Median (95%CI) | ||||
---|---|---|---|---|---|---|
qd Dose (µg) | 6‐h After Dose | |||||
10 | Day 1 | 9 |
737 (361‐1470) 806 (352) |
360 (215‐605) 380 (126) |
270 (7.00‐471) 267 (151) |
2.4 (−163.5 to 135.7) |
Day 13 | 9 |
883 (615‐1030) 860 (151) |
405 (177‐613) 375 (126) |
245 (−62.0 to 538) 262 (158) |
81.35 (−55.6 to 187.3) | |
30 | Day 1 | 6 |
1000 (737‐2060) 1210 (529) |
626 (469‐1070) 691 (238) |
595 (207‐892) 574 (244) |
392.8 (113.8‐623.6) |
Day 13 | 6 |
1330 (602‐2070) 1380 (557) |
649 (262‐1040) 607 (290) |
538 (248‐737) 490 (197) |
357.0 (140.8‐552.7) | |
30 (obese)a | Day 1 | 7 |
1040 (435‐1860) 1110 (495) |
518 (178‐918) 551 (242) |
460 (104‐845) 469 (237) |
299.70 (–37.5 to 649.3) |
Day 14 | 7 |
1050 (648‐1960) 1180 (447) |
479 (226‐877) 531 (238) |
418 (152‐752) 449 (217) |
117.05 (–285.7 to 304.10) | |
60 | Day 1 | 6 |
1370 (983‐3140) 1610 (780) |
581 (462‐847) 592 (137) |
456 (306‐706) 469 (138) |
323.2 (131.8‐490.6) |
Day 13 | 6 |
1140 (640‐2090) 1280 (612) |
597 (235‐829) 573 (230) |
475 (131‐735) 450 (258) |
237.5 (9.2‐529.4) | |
100 | Day 1 | 6 |
2320 (1310‐3190) 2240 (725) |
936 (428‐1660) 981 (424) |
731 (350‐1480) 821 (422) |
541.55 (254.80‐1094.0) |
Day 13 | 4 |
2290 (743‐4000) 2330 (1470) |
1150 (309‐1470) 1020 (502) |
1050 (231‐1290) 907 (469) |
671.65 (144.3‐1179.6) |
AUC0‐24h, area under the plasma concentration–time curve from time 0 to 24 h; Cmax, observed maximum plasma concentration following drug administration; CI, confidence interval; FGF19, fibroblast growth factor 19; MAD, multiple ascending dose; PD, pharmacodynamic; qd, once daily; SAD, single ascending dose.
Bolded values indicate P < .05 vs placebo by Wilcoxon rank‐sum test.
Day 14 assessment was performed in obese subjects instead of Day 13.