Table 3.
Changes in liver enzymes, biochemical concentrations, metabolic factors, and quality of life from baseline to 72 weeks
| Change from baseline to 72 weeks (mean [SD])
|
Mean changes from baseline* (obeticholic acid vs placebo) (95% CI) | p value* | ||
|---|---|---|---|---|
| Obeticholic acid (n=126) | Placebo (n=131) | |||
|
Liver enzymes
| ||||
| Alanine aminotransferase (U/L) | −38 (47) | −18 (44) | −20 (−28 to −11) | <0·0001 |
| Asparate aminotransferase (U/L) | −27 (37) | −10 (31) | −12 (−18 to −6) | 0·0001 |
| Alkaline phosphatase (U/L) | 12 (26) | −6 (20) | 18 (13 to 24) | <0·0001 |
| γ-glutamyl transpeptidase (U/L) | −37 (70) | −6 (48) | −24 (−35 to −14) | <0·0001 |
| Total bilirubin (μmol/L) | −1·0 (4·1) | 0·6 (3·7) | −1·5 (−2·4 to −0·5) | 0·002 |
|
| ||||
| Lipids | ||||
|
| ||||
| Total cholesterol (mmol/L) | 0·16 (1·07) | −0·19 (0·96) | 0·38 (0·16 to 0·60) | 0·0009 |
| HDL cholesterol (mmol/L) | −0·02 (0·20) | 0·03 (0·19) | −0·06 (−0·10 to −0·01) | 0·01 |
| LDL cholesterol (mmol/L) | 0·22 (0·90) | −0·22 (0·80) | 0·45 (0·26 to 0·65) | <0·0001 |
| Trigylcerides (mmol/L) | −0·22 (1·27) | −0·08 (1·74) | −0·02 (−0·35 to 0·30) | 0·88 |
|
| ||||
|
Haematology
| ||||
| Haemoglobin (g/L) | 0·6 (9·6) | 0·3 (9·5) | 0·4 (−1·8 to 2·6) | 0·72 |
| Haematocrit—proportion of 1·0 | 0·00 (0·03) | 0·00 (0·03) | 0·0 (−0·01 to 0·01) | 0·71 |
| Mean corpuscular volume (fL) | −0·8 (2·6) | 0·3 (3·5) | −1·1 (−1·8 to −0·4) | 0·002 |
| White blood cell count (109/L) | 0·0 (1·5) | 0·0 (1·1) | 0·1 (−0·2 to 0·4) | 0·40 |
| Platelet count (109/L) | 12 (33) | −4 (46) | 16 (7 to 26) | 0·001 |
|
| ||||
|
Chemistries
| ||||
| Bicarbonate (mmol/L) | −0·7 (3·2) | −0·1 (2·7) | −0·7 (−1·4 to −0·1) | 0·03 |
| Calcium (mmol/L) | 0·01 (0·10) | −0·01 (0·11) | 0·02 (0·00 to 0·04) | 0·04 |
| Phosphate (mmol/L) | 0·01 (0·18) | 0·02 (0·16) | 0·01 (−0·03 to 0·05) | 0·53 |
| Creatinine (μmol/L) | 1·5 (11·3) | −1·1 (9·6) | 2·6 (0·2 to 5·0) | 0·03 |
| Uric acid (μmol/L) | 2 (68) | −11 (56) | 14 (0 to 29) | 0·05 |
| Albumin (g/L) | −0·2 (3·1) | 0·3 (3·1) | −0·5 (−1·2 to 0·2) | 0·13 |
| Total protein (g/L) | 0·2 (4·5) | −0·5 (4·5) | 0·5 (−0·5 to 1·6) | 0·31 |
|
| ||||
|
Other laboratory results
| ||||
| Prothrombin time (s) | −0·1 (2·4) | 0·0 (2·2) | −0·2 (−0·6 to 0·1) | 0·16 |
| International normalised ratio | −0·03 (0·07) | 0·00 (0·08) | −0·02 (−0·04 to −0·01) | 0·002 |
|
| ||||
|
Metabolic factors
| ||||
| Fasting serum glucose (mmol/L) | 0·4 (2·1) | 0·2 (2·3) | 0·3 (−0·2 to 0·8) | 0·26 |
| Insulin (pmol/L) | 29 (159) | 10 (111) | 38 (6 to 69) | 0·02 |
| HOMA-IR (glucose [mmol/L] × insulin [pmol/L]/22·5) | 15 (50) | 4 (29) | 13 (3 to 23) | 0·01 |
| Glycated haemoglobin A1c (mmol/mol) | 0·5 (9·7) | 0·4 (8·3) | 0·4 (−1·7 to 2·6) | 0·71 |
| Weight (kg) | −2·3 (6·7) | 0·0 (6·1) | −2·2 (−3·7 to −0·6) | 0·008 |
| Body-mass index (kg/m2) | −0·7 (2·4) | 0·1 (2·2) | −0·7 (−1·3 to −0·2) | 0·01 |
| Waist circumference (cm) | −1·5 (7·1) | −0·6 (8·7) | −0·4 (−2·2 to 1·5) | 0·70 |
| Waist-to-hip ratio | 0·00 (0·06) | 0·00 (0·06) | 0·00 (−0·01 to 0·02) | 0·57 |
| Systolic blood pressure (mm Hg) | −4 (17) | −1 (16) | −3 (−7 to 0) | 0·05 |
| Diastolic blood pressure (mm Hg) | 0 (11) | 0 (10) | −1 (−4 to 1) | 0·23 |
|
| ||||
|
SF-36 Quality of life
| ||||
| Physical component summary | 0 (7) | −1 (7) | 1 (−1 to 3) | 0·22 |
| Mental component summary | 0 (9) | 1 (9) | 0 (−3 to 2) | 0·65 |
HOMA-IR=homoeostasis model assessment–estimated insulin resistance.
*
p values and mean changes from baseline were calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome.