Phase III, multicenter, randomized, double-blind, placebo-controlled study of norursodeoxycholic acid in metabolic dysfunction-associated steatotic liver disease patients

Table 1 Baseline demographic data, n (%)

Variables	norUDCA group (n = 108)	Placebo group (n = 55)
Mean age (years)	40.99 (10.51)	42.09 (11.94)
Gender
Female	16 (13.9)	10 (18.2)
Male	94 (86.1)	45 (81.8)
BMI	25.46 (3.46)	25.60 (3.44)

norUDCA: Norursodeoxycholic acid; BMI: Body mass index.

Table 2 Summary of patients achieved alanine aminotransferase normalization and improvements in the liver stiffness (using FibroScan) at week 12, n (%)

Visits	norUDCA group (n = 108)	Placebo group (n = 55)	P value
ALT normalization at week 12
Normalization	97 (89.8)	42 (76.4)	0.022
Abnormal	11 (10.2)	13 (23.6)
FibroScan stages at week 12
Improvement	62 (57.4)	22 (40.0)	0.035
No improvement	46 (42.6)	33 (34.5)

Normalization: Alanine aminotransferase ≤ 33 U/L for female and alanine aminotransferase ≤ 41 U/L for male; improvement: F2 to F0-F1; F3 to F0-F1; F3 to F2; No improvement: F2 to F2; F3 to F3. norUDCA: Norursodeoxycholic acid; ALT: Alanine aminotransferase.

Table 3 Summary of alanine aminotransferase in norursodeoxycholic acid and placebo groups at various visits, mean (95% confidence interval)

Visit	norUDCA	Placebo	P value
Visit 1/baseline	85.20 (81.34-89.06)	82.09 (77.37-86.82)	0.196
Visit 3/week 6	36.51 (28.88-44.24)	42.19 (31.49-52.89)	0.395
Visit 4/week 12	24.07 (21.01-27.13)	30.59 (26.31-34.89)	0.016
Visit 5/week 18	23.99 (20.54-27.46)	31.06 (26.21-35.92)	0.021
Visit 6/week 24	22.19 (18.13-26.25)	29.74 (24.04-35.44)	0.035

Mean of alanine aminotransferase are represented in U/L. norUDCA: Norursodeoxycholic acid.

Table 4 Summary of patients showing improvements in liver stiffness (using FibroScan) in norursodeoxycholic acid and placebo groups, mean (95% confidence interval)

Visits	norUDCA group (n = 108)	Placebo group (n = 55)	P value
Visit 4/week 12	7.46 (7.24-7.67)	8.02 (7.73-8.32)	0.002
Visit 6/week 24	6.46 (6.24-6.68)	7.12 (6.81-7.42)	0.001

norUDCA: Norursodeoxycholic acid.

Table 5 Summary of aspartate aminotransferase levels in norursodeoxycholic acid and placebo groups at various visits, mean (95% confidence interval)

Visit	norUDCA	Placebo	P value
Visit 1/baseline	87.01 (76.80-97.22)	92.29 (78.68-105.90)	0.551
Visit 3/week 6	32.52 (25.46-39.58)	42.25 (32.35-52.15)	0.116
Visit 4/week 12	28.26 (23.91-32.61)	32.17 (26.08-38.27)	0.304
Visit 5/week 18	24.69 (21.28-28.12)	30.34 (25.55-35.13)	0.060
Visit 6/week 24	25.84 (20.42-31.26)	32.36 (24.76-39.96)	0.170

Mean of aspartate aminotransferase are represented in U/L. norUDCA: Norursodeoxycholic acid.

Table 6 Summary of controlled attenuation parameter score in norursodeoxycholic acid and placebo groups at different time points

Visit	norUDCA		Placebo		P value	Change from baseline (P value)
	n	mean ± SD	n	mean ± SD
Baseline	72	276.21 ± 47.56	38	271.74 ± 39.04	0.62
Visit 4/week 12	72	243.40 ± 45.14	38	261.78 ± 50.4	0.054	0.003
Visit 6/week 24	72	228.04 ± 45.69	38	246.10 ± 42.74	0.014	0.005

Means are represented in dB/m. norUDCA: Norursodeoxycholic acid.

Table 7 Summary of adverse events, n (%)

Adverse events	norUDCA 1500 mg (n = 108)	Placebo (n = 55)
Patients with at least one TEAE	34 (30.9)	12 (21.81)
Total number of adverse events	42 (38.2)	14 (25.4)
Adverse events
Abdominal bloating	1 (0.93)	0
Abdominal pain	1 (0.93)	0
Abrasion	1 (0.93)	0
Acidity	0	1 (0.02)
Body pain	1 (0.93)	0
Cold	1 (0.93)	0
Constipation	3 (2.78)	0
Cough	1 (0.93)	0
Diabetes (hyperglycaemia)	3 (2.78)	1 (0.02)
Dyslipidaemia	15 (13.89)	3 (5.5)
Elevated liver enzymes	1 (0.93)	0
Epigastric pain	1 (0.93)	0
Fever	2 (1.85)	1 (0.02)
Gastric irritation	2 (1.85)	0
Headache	2 (1.85)	1 (0.02)
Hyperglycemia (impaired fasting glucose)	0	1 (0.02)
Loose stool	0	1 (0.02)
Mild thrombocytopenia	0	1 (0.02)
Nausea	0	1 (0.02)
Raised bilirubin	1 (0.93)	0
Rhinitis	1 (0.93)	0
Thrombocytopenia	1 (0.93)	0
Type 2 diabetes mellitus	4 (3.70)	3 (0.05)

norUDCA: Norursodeoxycholic acid; TEAE: Treatment-emergent adverse events.