New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial

Table 1 Baseline characteristics of the study population

Characteristic	High dose (n = 22)	Low dose (n = 23)	Placebo (n = 23)	P value
				High dose vs placebo	Low dose vs placebo
Age, yr	39.1 ± 9.5	45.5 ± 11.5	42.7 ± 11.2	0.474	0.355
Males, n (%)	20 (90.9)	14 (60.9)	20 (87.0)	1.0001	0.0441
Height, cm	170.1 ± 7.1	166.7 ± 10.3	170.4 ± 8.4	0.916	0.184
Weight, kg	82.4 ± 12.1	78.4 ± 16.0	82.9 ± 13.1	0.891	0.301
BMI, kg/m2	28.2 ± 3.4	28.2 ± 4.0	28.4 ± 3.7	0.805	0.855
Above moderate steatosis in US, n (%)	18 (81.8)	16 (69.6)	16 (69.6)	0.4911	1.000
MRS liver fat, %	16.1 ± 7.1	13.3 ± 7.1	12.0 ± 7.5	0.065	0.526
AST, IU/L	52.0 ± 19.1	58.4 ± 24.9	46.3 ± 20.5	0.461	0.077
ALT, IU/L	89.8 ± 34.8	90.3 ± 50.9	67.4 ± 32.7	0.109	0.078
Total cholesterol, mg/dL	205.0 ± 40.3	208.1 ± 31.2	194.5 ± 36.2	0.155	0.179
Triglyceride, mg/dL	190.3 ± 80.6	210.8 ± 137.9	286.7 ± 216.1	0.308	0.162
HDL cholesterol, mg/dL	46.3 ± 7.1	49.3 ± 10.9	43.6 ± 9.9	0.337	0.071
LDL cholesterol, mg/dL	136.0 ± 36.3	133.6 ± 29.7	118.6 ± 30.7	0.053	0.099
VLDL cholesterol, mg/dL	22.7 ± 11.2	25.3 ± 16.3	32.4 ± 21.5	0.263	0.214
Free fatty acid, μEq/L	526.2 ± 209.5	523.7 ± 341.6	581.9 ± 634.7	0.135	0.700
HOMA-IR	2.6 ± 1.6	2.5 ± 1.0	3.5 ± 2.4	0.167	0.3262

¹Fisher’s exact test;

²Wilcoxon’s rank sum test. Continuous data are expressed as mean ± SD. Categorical data are expressed as n (%). BMI: Body mass index; US: Ultrasonography; MRS: Magnetic resonance spectroscopy; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HDL: High density lipoprotein cholesterol; LDL: Low density lipoprotein cholesterol; VLDL: Very low density lipoprotein cholesterol; HOMA-IR: Homeostasis model assessment-estimated insulin resistance.

Table 2 Change of hepatic fat content from baseline after 12 wk of treatment

Treatment group	Full analysis set				Per protocol set
	n	Baseline	12 wk	P value	n	Baseline	12 wk	P value
Placebo, %	23	11.96 ± 7.46	12.57 ± 8.34		20	12.59 ± 7.70	13.59 ± 8.47
Low dose, %	23	13.33 ± 7.11	12.12 ± 6.33	0.3861	20	12.99 ± 6.86	11.37 ± 6.02	0.1641
High dose, %	22	16.05 ± 7.05	14.34 ± 7.19	0.0332	20	16.12 ± 7.19	14.77 ± 7.15	0.0392

¹Two sample t-test;

²Wilcoxon’s rank sum test. Continuous data are expressed as mean ± SD.

Table 3 Secondary endpoint changes from baseline after 12 wk of treatment (full analysis set)

Variable	High dose (n = 22)	Low dose (n = 23)	Placebo (n = 23)	P value
				High dose vs placebo	Low dose vs placebo
AST, IU/L	-7.82 ± 20.59	-2.74 ± 33.79	-2.96 ± 21.19	0.865	0.397
ALT, IU/L	-12.73 ± 29.30	-13.65 ± 39.56	-0.17 ± 19.58	0.097	0.153
Total cholesterol, mg/dL	-7.86 ± 27.92	2.22 ± 32.89	-0.61 ± 22.47	0.532	0.613
Triglyceride, mg/dL	-16.50 ± 52.47	29.57 ± 186.19	-86.91 ± 157.20	0.041	0.031
HDL cholesterol, mg/dL	1.32 ± 14.98	-1.78 ± 8.71	1.83 ± 8.62	0.289	0.567
LDL cholesterol, mg/dL	9.05 ± 27.78	-5.35 ± 23.63	5.74 ± 19.98	0.088	0.253
VLDL cholesterol, mg/dL	0.43 ± 12.05	9.52 ± 27.85	-9.77 ± 17.47	0.047	0.007
Free fatty acid, μEq/L	-73.23 ± 283.52	15.70 ± 304.68	-73.87 ± 666.93	0.146	0.921
HOMA IR	-0.01 ± 1.41	0.18 ± 0.77	-1.32 ± 2.44	0.174	0.019
BMI, kg/m2	0.01 ± 0.81	-0.06 ± 0.97	-0.20 ± 0.80	0.608	0.904

Continuous data are expressed as mean ± SD. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HDL: High density lipoprotein cholesterol; LDL: Low density lipoprotein cholesterol; VLDL: Very low density lipoprotein cholesterol; HOMA-IR: Homeostasis model assessment-estimated insulin resistance.

Table 4 Treatment-related adverse events during the study n (%)

System organ class preferred term	High dose (n = 23)	Low dose (n = 26)	Placebo (n = 24)
Gastrointestinal disorders
Abdominal pain upper	0	1 (3.85)	0 (0)
Nausea	0	0 (0)	1 (4.17)
Nervous system disorders
Dizziness	0	1 (3.85)	0 (0)