Safety, tolerability and pharmacodynamics of apical sodium-dependent bile acid transporter inhibition with volixibat in healthy adults and patients with type 2 diabetes mellitus: a randomised placebo-controlled trial

Table 3 Summary of serum bile acids and serum markers of bile acid synthesis/metabolism

	Day	Number	Serum bile acid (μmol/L)		C4 (ng/mL)		FGF-19 (pg/mL)		FGF-21 (pg/mL)
	Day	Number	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Healthy volunteers
Placebo	1	12	4.676	3.3066	29.95	12.917	359.2	500.55	174.1	90.84
	14	12	2.941	2.2596	15.21	12.211	264.3	280.50	224.2	180.73
	28	12	2.951	2.3758	15.23	8.537	259.3	333.54	167.6	112.15
Volixibat 0.5 mg	1	10	5.886	4.2363	22.87	6.427	304.8	328.52	195.6	155.49
	14	10	2.304	1.6197	35.57	25.119	297.0	302.87	219.7	133.12
	28	9	2.540	1.9897	30.21	13.358	306.7	247.72	204.6	104.43
Volixibat 1 mg	1	9	5.614	5.7738	14.49	5.304	495.3	969.34	138.9	118.64
	14	9^a	4.176	3.9589	23.60	13.736	551.1	1129.55	206.6	195.40
	28	9^a	1.838	0.9931	24.92	14.686	1056.7	2428.36	150.2	99.92
Volixibat 5 mg	1	8	2.826	1.4719	30.78	19.365	669.0	1301.49	224.0	111.03
	14	8	1.861	1.4777	56.38	43.306	651.4	1324.94	252.3	146.26
	28	6	2.872	1.6163	56.52	38.863	784.7	1405.55	215.2	142.22
Volixibat 10 mg	1	8	2.248	1.7120	13.75	4.602	228.1	239.87	204.1	156.90
	14	8	1.959	1.1725	37.51	18.886	186.6	242.72	253.9	165.21
	28	8	1.743	0.9222	72.86	35.499	164.6	226.91	212.6	157.95
Patients with T2DM
Placebo	1	3^b	2.370	1.6532	16.60	6.899	211.5	212.84	360.0	300.66
	14	3	2.523	2.2756	14.40	3.568	94.3	121.25	463.0	386.47
	28	3^b	1.340	0.1758	28.73	8.545	173.5	197.28	309.3	184.02
Volixibat 10 mg	1	8	1.826	1.6175	30.15	14.351	605.8	1264.78	334.0	128.76
	14	8^c	2.355	1.1042	59.66	28.221	640.1	1399.18	497.9	198.04
	28	8	2.118	0.9359	61.81	22.163	114.4	146.91	359.0	178.13

C4 7α-hydroxy-4-cholesten-3-one, FGF fibroblast growth factor, N number of patients for whom data were available, SD standard deviation, T2DM type 2 diabetes mellitus
On day 1 (baseline), measurements were taken before participants received the first dose of study drug. Data are from the pharmacodynamic analysis set
^aFibroblast growth factor data available for 8 patients on day 14 and 7 patients on day 28. ^bFibroblast growth factor data available for 2 patients on day 1 and 2 patients on day 28. ^cFibroblast growth factor data available for 7 patients on day 14

ISSN: 1471-230X