Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis (NASH)
Conditions
Keywords
Farnesoid X Receptor, FXR, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, NAFLD, NASH, obeticholic acid
Brief summary
Administration of the farnesoid X receptor (FXR) ligand obeticholic acid (OCA) for 72 weeks to subjects with biopsy evidence of nonalcoholic steatohepatitis (NASH) will result in improvement in their liver disease as measured by changes in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS).
Detailed description
To evaluate whether treatment with obeticholic acid, 25 mg daily for 72 weeks compared to treatment with placebo, improves the severity of nonalcoholic fatty liver disease (NAFLD) as determined from hepatic histology.
Interventions
DRUGobeticholic acid
25 mg daily for 72 weeks
DRUGplacebo
placebo capsule, 25 mg daily for 72 weeks
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older as of the initial screening interview and provision of consent * Histologic evidence of definite or probable nonalcoholic steatohepatitis (NASH) based upon a liver biopsy obtained no more than 90 days prior to randomization and a nonalcoholic fatty liver disease activity score (NAS) of 4 or greater with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).
Exclusion criteria
* Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males, on average) * Inability to reliably quantify alcohol consumption based upon local study physician judgment * Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the year prior to randomization * Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass) * Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher within 60 days prior to enrollment * Presence of cirrhosis on liver biopsy * A platelet count below 100,000/mm3 * Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities: * Serum albumin less than 3.2 grams/deciliter (g/dL) * International Normalized Ratio(INR)greater than 1.3 * Direct bilirubin greater than 1.3 milligrams per deciliter (mg/dL) * History of esophageal varices, ascites or hepatic encephalopathy * Evidence of other forms of chronic liver disease: * Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg) * Hepatitis C as defined by presence of hepatitis C virus (HCV) ribonucleic acid (RNA) or positive hepatitis C antibody (anti-HCV) * Evidence of ongoing autoimmune liver disease as defined by compatible liver histology * Primary biliary cirrhosis as defined by the presence of at least 2 of these criteria (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii)Presence of anti-mitochondrial antibody (AMA) (iii)Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts * Primary sclerosing cholangitis * Wilson's disease as defined by ceruloplasmin below the limits of normal and compatible liver histology * Alpha-1-antitrypsin(A1AT) deficiency as defined by diagnostic features in liver histology (confirmed by alpha-1 antitrypsin level less than normal; exclusion at the discretion of the study physician) * History of hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy * Drug-induced liver disease as defined on the basis of typical exposure and history * Known bile duct obstruction * Suspected or proven liver cancer * Any other type of liver disease other than nonalcoholic steatohepatitis (NASH) * Serum alanine aminotransferase (ALT) greater than 300 units per liter (U/L) * Serum creatinine of 2.0 mg/dL or greater * Use of ursodeoxycholic acid (Ursodiol, Urso) within 90 days prior to enrollment * Inability to safely obtain a liver biopsy * History of biliary diversion * Known positivity for Human Immunodeficiency Virus (HIV) infection * Active, serious medical disease with likely life expectancy less than 5 years * Active substance abuse including inhaled or injection drugs in the year prior to screening * Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding * Participation in an investigational new drug (IND) trial in the 30 days before randomization * Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study * Failure to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | baseline to 72 weeks | Centrally scored histological improvement in nonalcoholic fatty liver disease (NAFLD) from baseline to the end of 72 weeks of treatment, where improvement is defined as: 1. No worsening in fibrosis; and 2. A decrease in NAFLD Activity Score (NAS) of at least 2 points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fibrosis: Patient With Improvement | baseline to 72 weeks | Patients with improvement in fibrosis score. Fibrosis was assessed on a scale of 0-4, with higher scores showing more severe fibrosis. |
| Fibrosis: Change in Score | baseline to 72 weeks | Change in fibrosis score. Fibrosis was assessed on a scale of 0-4, with higher scores showing more severe fibrosis. |
| Total NAFLD Activity Score: Change in Score | baseline to 72 weeks | NAFLD activity score was assessed on a scale of 0-8, with higher scores showing more severe disease (the components of this measure are steatosis \[assessed on a scale of 0-3\], lobular inflammation \[assessed on a scale of 0-3\], and hepatocellular ballooning \[assessed on a scale of 0-2\]). |
| Hepatocellular Ballooning: Patients With Improvement | baseline to 72 weeks | Patients with improvement in hepatocellular ballooning score. Hepatocellular ballooning was assessed on a scale of 0-2, with higher scores showing more severe ballooning. |
| Hepatocellular Ballooning: Change in Score | baseline to 72 weeks | Change in hepatocellular ballooning score. Hepatocellular ballooning was assessed on a scale of 0-2, with higher scores showing more severe ballooning. |
| Steatosis: Patients With Improvement | baseline to 72 weeks | Patients with improvement in steatosis score. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis. |
| Steatosis: Change in Score | baseline to 72 weeks | Change in steatosis score. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis. |
| Lobular Inflammation: Patients With Improvement | baseline to 72 weeks | Patients with improvement in lobular inflammation score. Lobular inflammation was assessed on a scale of 0-3, with higher scores showing more severe lobular inflammation. |
| Lobular Inflammation: Change in Score | baseline to 72 weeks | Change in lobular inflammation score. Lobular inflammation was assessed on a scale of 0-3, with higher scores showing more severe lobular inflammation. |
| Portal Inflammation: Patients With Improvement | baseline to 72 weeks | Patients with improvement in portal inflammation score. Portal inflammation was assessed on a scale of 0-2, with higher scores showing more severe portal inflammation. |
| Portal Inflammation: Change in Score | baseline to 72 weeks | Change in portal inflammation score. Portal inflammation was assessed on a scale of 0-3, with higher scores showing more severe portal inflammation. |
| Change in Alanine Aminotransferase | baseline to 72 weeks | — |
| Change in Asparate Aminotransferase | baseline to 72 weeks | — |
| Change in Alkaline Phosphatase | baseline to 72 weeks | — |
| Change in γ-glutamyl Transpeptidase | baseline to 72 weeks | — |
| Change in Total Bilirubin | baseline to 72 weeks | — |
| Change in Total Cholesterol | baseline to 72 weeks | — |
| Change in HDL Cholesterol | baseline to 72 weeks | — |
| Change in LDL Cholesterol | baseline to 72 weeks | — |
| Change in Triglycerides | baseline to 72 weeks | — |
| Change in Haemoglobin | baseline to 72 weeks | — |
| Change in Haematocrit | baseline to 72 weeks | — |
| Change in Mean Corpuscular Volume | baseline to 72 weeks | — |
| Change in White Blood Cell Count | baseline to 72 weeks | — |
| Change in Platelet Count | baseline to 72 weeks | — |
| Change in Bicarbonate | baseline to 72 weeks | — |
| Change in Calcium | baseline to 72 weeks | — |
| Change in Phosphate | baseline to 72 weeks | — |
| Change in Creatinine | baseline to 72 weeks | — |
| Change in Uric Acid | baseline to 72 weeks | — |
| Change in Albumin | baseline to 72 weeks | — |
| Change in Total Protein | baseline to 72 weeks | — |
| Change in Prothrombin Time | baseline to 72 weeks | — |
| Change in International Normalised Ratio | baseline to 72 weeks | — |
| Change in Fasting Serum Glucose | baseline to 72 weeks | — |
| Change in Insulin | baseline to 72 weeks | — |
| Change in HOMA-IR | baseline to 72 weeks | — |
| Change in Glycated Haemoglobin A1c | baseline to 72 weeks | — |
| Change in Weight | baseline to 72 weeks | — |
| Change in Body-mass Index | baseline to 72 weeks | — |
| Resolution of NASH Diagnosis | baseline to 72 weeks | Resolution of definite nonalcoholic steatohepatitis. Resolution defined as either not NAFLD, or NAFLD but not non-alcoholic steatohepatitis on week 72 biopsy |
| Change in Waist-to-hip Ratio | baseline to 72 weeks | — |
| Change in Systolic Blood Pressure | baseline to 72 weeks | — |
| Change in Diastolic Blood Pressure | baseline to 72 weeks | — |
| Change in SF-36 Quality of Life Physical Component Summary | baseline to 72 weeks | Short Form (36) Health Survey The SF-36 evaluates health-related quality of life in 8 domains consisting of two components: physical and mental. The score for each domain ranges from 0 to 100. Norm based scoring (based on the general US population) is used with a mean of 50 and standard deviation of 10. Higher values represent a better outcome. |
| Change in SF-36 Quality of Life Mental Component Summary | baseline to 72 weeks | Short Form (36) Health Survey The SF-36 evaluates health-related quality of life in 8 domains consisting of two components: physical and mental. The score for each domain ranges from 0 to 100. Norm based scoring (based on the general US population) is used with a mean of 50 and standard deviation of 10. Higher values represent a better outcome. |
| Change in Waist Circumference | baseline to 72 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Obeticholic Acid obeticholic acid
obeticholic acid: 25 mg daily for 72 weeks | 141 |
| Placebo Placebo
placebo: placebo capsule, 25 mg daily for 72 weeks | 142 |
| Total | 283 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol modified to eliminate wk72 bx | 31 | 33 |
Baseline characteristics
| Characteristic | Total | Placebo | Obeticholic Acid |
|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 11 | 51 years STANDARD_DEVIATION 12 | 52 years STANDARD_DEVIATION 11 |
| Chemistries: Albumin | 43 g/L STANDARD_DEVIATION 4 | 43 g/L STANDARD_DEVIATION 4 | 43 g/L STANDARD_DEVIATION 4 |
| Chemistries: Bicarbonate | 26.0 mmol/L STANDARD_DEVIATION 2.5 | 26.2 mmol/L STANDARD_DEVIATION 2.6 | 25.9 mmol/L STANDARD_DEVIATION 2.5 |
| Chemistries: Calcium | 2.4 mmol/L STANDARD_DEVIATION 0.1 | 2.4 mmol/L STANDARD_DEVIATION 0.1 | 2.4 mmol/L STANDARD_DEVIATION 0.1 |
| Chemistries: Creatinine | 71 μmol/L STANDARD_DEVIATION 17 | 70 μmol/L STANDARD_DEVIATION 16 | 71 μmol/L STANDARD_DEVIATION 18 |
| Chemistries: Phosphate | 1.1 mmol/L STANDARD_DEVIATION 0.2 | 1.1 mmol/L STANDARD_DEVIATION 0.2 | 1.1 mmol/L STANDARD_DEVIATION 0.2 |
| Chemistries: Total protein | 73 g/L STANDARD_DEVIATION 5 | 74 g/L STANDARD_DEVIATION 5 | 73 g/L STANDARD_DEVIATION 5 |
| Chemistries: Uric acid | 370 μmol/L STANDARD_DEVIATION 87 | 366 μmol/L STANDARD_DEVIATION 86 | 375 μmol/L STANDARD_DEVIATION 89 |
| Comorbidities: Cardiovascular disease | 15 participants | 8 participants | 7 participants |
| Comorbidities: Diabetes | 149 participants | 74 participants | 75 participants |
| Comorbidities: Hyperlipidaemia | 173 participants | 86 participants | 87 participants |
| Comorbidities: Hypertension | 172 participants | 85 participants | 87 participants |
| Concomitant medications in the past 6 months: Antidiabetic | 140 participants | 73 participants | 67 participants |
| Concomitant medications in the past 6 months: Antilipidaemic | 136 participants | 64 participants | 72 participants |
| Concomitant medications in the past 6 months: Aspirin (81 mg) | 70 participants | 33 participants | 37 participants |
| Concomitant medications in the past 6 months: Cardiovascular | 189 participants | 92 participants | 97 participants |
| Concomitant medications in the past 6 months: Metformin | 117 participants | 62 participants | 55 participants |
| Concomitant medications in the past 6 months: Pioglitazone | 7 participants | 6 participants | 1 participants |
| Concomitant medications in the past 6 months: Thiazolidinedione | 8 participants | 5 participants | 3 participants |
| Concomitant medications in the past 6 months: Vitamin E | 61 participants | 32 participants | 29 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants | 21 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 240 Participants | 121 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Haematology: Haematocrit | 0.41 proportion of 1·0 STANDARD_DEVIATION 0.04 | 0.41 proportion of 1·0 STANDARD_DEVIATION 0.04 | 0.41 proportion of 1·0 STANDARD_DEVIATION 0.04 |
| Haematology: Haemoglobin | 140 g/L STANDARD_DEVIATION 14 | 140 g/L STANDARD_DEVIATION 14 | 140 g/L STANDARD_DEVIATION 15 |
| Haematology: Mean corpuscular volume | 88.9 fL STANDARD_DEVIATION 5.1 | 89.0 fL STANDARD_DEVIATION 5.3 | 88.7 fL STANDARD_DEVIATION 4.8 |
| Haematology: Platelet count | 237 platelets *10^9 per L STANDARD_DEVIATION 62 | 237 platelets *10^9 per L STANDARD_DEVIATION 65 | 237 platelets *10^9 per L STANDARD_DEVIATION 59 |
| Haematology: White blood cell count | 7.1 white blood cells *10^9 per L STANDARD_DEVIATION 2.1 | 6.9 white blood cells *10^9 per L STANDARD_DEVIATION 2.3 | 7.3 white blood cells *10^9 per L STANDARD_DEVIATION 1.9 |
| Lipids: HDL cholesterol | 1.1 mmol/L STANDARD_DEVIATION 0.3 | 1.1 mmol/L STANDARD_DEVIATION 0.4 | 1.1 mmol/L STANDARD_DEVIATION 0.3 |
| Lipids: LDL cholesterol | 2.9 mmol/L STANDARD_DEVIATION 1 | 2.9 mmol/L STANDARD_DEVIATION 1.1 | 2.9 mmol/L STANDARD_DEVIATION 1 |
| Lipids: Total cholesterol | 4.9 mmol/L STANDARD_DEVIATION 1.2 | 4.8 mmol/L STANDARD_DEVIATION 1.2 | 4.9 mmol/L STANDARD_DEVIATION 1.2 |
| Lipids: Triglycerides | 2.1 mmol/L STANDARD_DEVIATION 1.6 | 2.0 mmol/L STANDARD_DEVIATION 1.7 | 2.2 mmol/L STANDARD_DEVIATION 1.5 |
| Liver enzymes: Alanine aminotransferase | 83 U/L STANDARD_DEVIATION 50 | 82 U/L STANDARD_DEVIATION 51 | 83 U/L STANDARD_DEVIATION 49 |
| Liver enzymes: Alkaline phosphatase | 82 U/L STANDARD_DEVIATION 27 | 81 U/L STANDARD_DEVIATION 25 | 82 U/L STANDARD_DEVIATION 29 |
| Liver enzymes: Aspartate aminotransferase | 61 U/L STANDARD_DEVIATION 36 | 58 U/L STANDARD_DEVIATION 34 | 64 U/L STANDARD_DEVIATION 38 |
| Liver enzymes: Total bilirubin | 11.4 μmol/L STANDARD_DEVIATION 6.8 | 11.3 μmol/L STANDARD_DEVIATION 7.5 | 11.5 μmol/L STANDARD_DEVIATION 5.9 |
| Liver enzymes: γ-glutamyl transpeptidase | 77 U/L STANDARD_DEVIATION 91 | 76 U/L STANDARD_DEVIATION 97 | 78 U/L STANDARD_DEVIATION 85 |
| Liver histology findings: Biopsy length | 21 mm STANDARD_DEVIATION 10 | 21 mm STANDARD_DEVIATION 10 | 21 mm STANDARD_DEVIATION 10 |
| Liver histology findings: Definite steatohepatitis | 225 participants | 111 participants | 114 participants |
| Liver histology findings: Fibrosis stage | 1.8 units on a scale STANDARD_DEVIATION 1.1 | 1.8 units on a scale STANDARD_DEVIATION 1 | 1.9 units on a scale STANDARD_DEVIATION 1.1 |
| Liver histology findings: Hepatocellular ballooning score | 1.4 units on a scale STANDARD_DEVIATION 0.7 | 1.3 units on a scale STANDARD_DEVIATION 0.7 | 1.4 units on a scale STANDARD_DEVIATION 0.7 |
| Liver histology findings: Lobular inflammation score | 1.8 units on a scale STANDARD_DEVIATION 0.7 | 1.8 units on a scale STANDARD_DEVIATION 0.7 | 1.8 units on a scale STANDARD_DEVIATION 0.7 |
| Liver histology findings: Portal inflammation score | 1.1 units on a scale STANDARD_DEVIATION 0.6 | 1.1 units on a scale STANDARD_DEVIATION 0.6 | 1.2 units on a scale STANDARD_DEVIATION 0.6 |
| Liver histology findings: Steatosis score | 2.0 units on a scale STANDARD_DEVIATION 0.8 | 2.0 units on a scale STANDARD_DEVIATION 0.8 | 2.1 units on a scale STANDARD_DEVIATION 0.8 |
| Liver histology findings: Total NAFLD activity score | 5.2 units on a scale STANDARD_DEVIATION 1.3 | 5.1 units on a scale STANDARD_DEVIATION 1.3 | 5.3 units on a scale STANDARD_DEVIATION 1.3 |
| Metabolic factors: Body-mass index | 35 kg/m² STANDARD_DEVIATION 6 | 34 kg/m² STANDARD_DEVIATION 6 | 35 kg/m² STANDARD_DEVIATION 7 |
| Metabolic factors: Diastolic blood pressure | 77 mm Hg STANDARD_DEVIATION 10 | 78 mm Hg STANDARD_DEVIATION 10 | 77 mm Hg STANDARD_DEVIATION 11 |
| Metabolic factors: Fasting serum glucose | 6.4 mmol/L STANDARD_DEVIATION 2 | 6.4 mmol/L STANDARD_DEVIATION 2.2 | 6.5 mmol/L STANDARD_DEVIATION 1.8 |
| Metabolic factors: Glycated haemoglobin A1c | 47 mmol/mol STANDARD_DEVIATION 11 | 47 mmol/mol STANDARD_DEVIATION 11 | 48 mmol/mol STANDARD_DEVIATION 12 |
| Metabolic factors: HOMA-IR | 50 glucose [mmol/L] × insulin [pmol/L]/22.5 STANDARD_DEVIATION 61 | 40 glucose [mmol/L] × insulin [pmol/L]/22.5 STANDARD_DEVIATION 42 | 61 glucose [mmol/L] × insulin [pmol/L]/22.5 STANDARD_DEVIATION 74 |
| Metabolic factors: Insulin | 169 pmol/L STANDARD_DEVIATION 186 | 138 pmol/L STANDARD_DEVIATION 129 | 201 pmol/L STANDARD_DEVIATION 226 |
| Metabolic factors: Systolic blood pressure | 132 mm Hg STANDARD_DEVIATION 16 | 132 mm Hg STANDARD_DEVIATION 15 | 132 mm Hg STANDARD_DEVIATION 17 |
| Metabolic factors: Waist circumference | 111 cm STANDARD_DEVIATION 15 | 109 cm STANDARD_DEVIATION 14 | 112 cm STANDARD_DEVIATION 15 |
| Metabolic factors: Waist-to-hip ratio | 0.95 ratio STANDARD_DEVIATION 0.08 | 0.95 ratio STANDARD_DEVIATION 0.09 | 0.96 ratio STANDARD_DEVIATION 0.07 |
| Metabolic factors: Weight | 98 kg STANDARD_DEVIATION 21 | 96 kg STANDARD_DEVIATION 18 | 100 kg STANDARD_DEVIATION 23 |
| Other laboratory results: International normalised ratio | 1.00 ratio STANDARD_DEVIATION 0.07 | 1.00 ratio STANDARD_DEVIATION 0.07 | 1.01 ratio STANDARD_DEVIATION 0.08 |
| Other laboratory results: Prothrombin time | 11.7 s STANDARD_DEVIATION 2.1 | 11.7 s STANDARD_DEVIATION 2.2 | 11.7 s STANDARD_DEVIATION 2.1 |
| Race/Ethnicity, Customized Asian | 16 participants | 10 participants | 6 participants |
| Race/Ethnicity, Customized Black or African-American | 6 participants | 4 participants | 2 participants |
| Race/Ethnicity, Customized Other | 27 participants | 17 participants | 10 participants |
| Race/Ethnicity, Customized White | 234 participants | 111 participants | 123 participants |
| Sex: Female, Male Female | 187 Participants | 89 Participants | 98 Participants |
| Sex: Female, Male Male | 96 Participants | 53 Participants | 43 Participants |
| SF-36 Quality of life: Mental component summary | 48 units on a scale STANDARD_DEVIATION 12 | 48 units on a scale STANDARD_DEVIATION 12 | 48 units on a scale STANDARD_DEVIATION 12 |
| SF-36 Quality of life: Physical component summary | 44 units on a scale STANDARD_DEVIATION 11 | 44 units on a scale STANDARD_DEVIATION 11 | 45 units on a scale STANDARD_DEVIATION 11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 99 / 141 | 68 / 142 |
| serious Total, serious adverse events | 13 / 141 | 10 / 142 |
Outcome results
Primary
Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Centrally scored histological improvement in nonalcoholic fatty liver disease (NAFLD) from baseline to the end of 72 weeks of treatment, where improvement is defined as: 1. No worsening in fibrosis; and 2. A decrease in NAFLD Activity Score (NAS) of at least 2 points
Time frame: baseline to 72 weeks
Population: Number of randomly assigned patients with observed or expected week 72 visit before protocol modified on Jan 6, 2014, to eliminate week 72 biopsy. 11 patients in the placebo group and eight in the obeticholic acid group had missing histological data at week 72, and the results for these patients were imputed as a lack of improvement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | 50 participants |
| Placebo | Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) | 23 participants |
p-value: 0.000295% CI: [1.3, 2.8]Cochran-Mantel-Haenszel
Secondary
Change in Alanine Aminotransferase
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Alanine Aminotransferase | -38 U/L | Standard Deviation 47 |
| Placebo | Change in Alanine Aminotransferase | -18 U/L | Standard Deviation 44 |
p-value: <0.000195% CI: [-28, -11]ANCOVA
Secondary
Change in Albumin
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Albumin | -0.2 gl/L | Standard Deviation 3.1 |
| Placebo | Change in Albumin | 0.3 gl/L | Standard Deviation 3.1 |
p-value: 0.1395% CI: [-1.2, 0.2]ANCOVA
Secondary
Change in Alkaline Phosphatase
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Alkaline Phosphatase | 12 U/L | Standard Deviation 26 |
| Placebo | Change in Alkaline Phosphatase | -6 U/L | Standard Deviation 20 |
p-value: <0.000195% CI: [13, 24]ANCOVA
Secondary
Change in Asparate Aminotransferase
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Asparate Aminotransferase | -27 U/L | Standard Deviation 37 |
| Placebo | Change in Asparate Aminotransferase | -10 U/L | Standard Deviation 31 |
p-value: 0.000195% CI: [-18, -6]ANCOVA
Secondary
Change in Bicarbonate
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Bicarbonate | -0.7 mmol/L | Standard Deviation 3.2 |
| Placebo | Change in Bicarbonate | -0.1 mmol/L | Standard Deviation 2.7 |
p-value: 0.0395% CI: [-1.4, -0.1]ANCOVA
Secondary
Change in Body-mass Index
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Body-mass Index | -0.7 kg/m² | Standard Deviation 2.4 |
| Placebo | Change in Body-mass Index | 0.1 kg/m² | Standard Deviation 2.2 |
p-value: 0.0195% CI: [-1.3, -0.2]ANCOVA
Secondary
Change in Calcium
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Calcium | 0.01 mmol/L | Standard Deviation 0.1 |
| Placebo | Change in Calcium | -0.01 mmol/L | Standard Deviation 0.11 |
p-value: 0.0495% CI: [0, 0.04]ANCOVA
Secondary
Change in Creatinine
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Creatinine | 1.5 μmol/L | Standard Deviation 11.3 |
| Placebo | Change in Creatinine | -1.1 μmol/L | Standard Deviation 9.6 |
p-value: 0.0395% CI: [0.2, 5]ANCOVA
Secondary
Change in Diastolic Blood Pressure
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Diastolic Blood Pressure | 0 mm Hg | Standard Deviation 11 |
| Placebo | Change in Diastolic Blood Pressure | 0 mm Hg | Standard Deviation 10 |
p-value: 0.2395% CI: [-4, 1]ANCOVA
Secondary
Change in Fasting Serum Glucose
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Fasting Serum Glucose | 0.4 mmol/L | Standard Deviation 2.1 |
| Placebo | Change in Fasting Serum Glucose | 0.2 mmol/L | Standard Deviation 2.3 |
p-value: 0.2695% CI: [-0.2, 0.8]ANCOVA
Secondary
Change in Glycated Haemoglobin A1c
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Glycated Haemoglobin A1c | 0.5 mmol/mol | Standard Deviation 9.7 |
| Placebo | Change in Glycated Haemoglobin A1c | 0.4 mmol/mol | Standard Deviation 8.3 |
p-value: 0.7195% CI: [-1.7, 2.6]ANCOVA
Secondary
Change in Haematocrit
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Haematocrit | 0.00 proportion of 1.0 | Standard Deviation 0.03 |
| Placebo | Change in Haematocrit | 0.00 proportion of 1.0 | Standard Deviation 0.03 |
p-value: 0.7195% CI: [-0.01, 0.01]ANCOVA
Secondary
Change in Haemoglobin
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Haemoglobin | 0.6 g/L | Standard Deviation 9.6 |
| Placebo | Change in Haemoglobin | 0.3 g/L | Standard Deviation 9.5 |
p-value: 0.7295% CI: [-1.8, 2.6]ANCOVA
Secondary
Change in HDL Cholesterol
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in HDL Cholesterol | -0.02 mmol/L | Standard Deviation 0.2 |
| Placebo | Change in HDL Cholesterol | 0.03 mmol/L | Standard Deviation 0.19 |
p-value: 0.0195% CI: [-0.1, -0.01]ANCOVA
Secondary
Change in HOMA-IR
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in HOMA-IR | 15 glucose[mmol/L]× insulin[pmol/L] / 22.5 | Standard Deviation 50 |
| Placebo | Change in HOMA-IR | 4 glucose[mmol/L]× insulin[pmol/L] / 22.5 | Standard Deviation 29 |
p-value: 0.0195% CI: [3, 23]ANCOVA
Secondary
Change in Insulin
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Insulin | 29 pmol/L | Standard Deviation 159 |
| Placebo | Change in Insulin | 10 pmol/L | Standard Deviation 111 |
p-value: 0.0295% CI: [6, 69]ANCOVA
Secondary
Change in International Normalised Ratio
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in International Normalised Ratio | -0.03 ratio | Standard Deviation 0.07 |
| Placebo | Change in International Normalised Ratio | 0.00 ratio | Standard Deviation 0.08 |
p-value: 0.00295% CI: [-0.04, -0.01]ANCOVA
Secondary
Change in LDL Cholesterol
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in LDL Cholesterol | 0.22 mmol/L | Standard Deviation 0.9 |
| Placebo | Change in LDL Cholesterol | -0.22 mmol/L | Standard Deviation 0.8 |
p-value: <0.000195% CI: [0.26, 0.65]ANCOVA
Secondary
Change in Mean Corpuscular Volume
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Mean Corpuscular Volume | -0.8 fL | Standard Deviation 2.6 |
| Placebo | Change in Mean Corpuscular Volume | 0.3 fL | Standard Deviation 3.5 |
p-value: 0.00295% CI: [-1.8, -0.4]ANCOVA
Secondary
Change in Phosphate
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Phosphate | 0.01 mmol/L | Standard Deviation 0.18 |
| Placebo | Change in Phosphate | 0.02 mmol/L | Standard Deviation 0.16 |
p-value: 0.5395% CI: [-0.03, 0.05]ANCOVA
Secondary
Change in Platelet Count
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Platelet Count | 12 platelets *10^9 per L | Standard Deviation 33 |
| Placebo | Change in Platelet Count | -4 platelets *10^9 per L | Standard Deviation 46 |
p-value: 0.00195% CI: [7, 26]ANCOVA
Secondary
Change in Prothrombin Time
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Prothrombin Time | -0.1 s | Standard Deviation 2.4 |
| Placebo | Change in Prothrombin Time | 0.0 s | Standard Deviation 2.2 |
p-value: 0.1695% CI: [-0.6, 0.1]ANCOVA
Secondary
Change in SF-36 Quality of Life Mental Component Summary
Short Form (36) Health Survey The SF-36 evaluates health-related quality of life in 8 domains consisting of two components: physical and mental. The score for each domain ranges from 0 to 100. Norm based scoring (based on the general US population) is used with a mean of 50 and standard deviation of 10. Higher values represent a better outcome.
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in SF-36 Quality of Life Mental Component Summary | 0 units on a scale | Standard Deviation 9 |
| Placebo | Change in SF-36 Quality of Life Mental Component Summary | 1 units on a scale | Standard Deviation 9 |
p-value: 0.6595% CI: [-3, 2]ANCOVA
Secondary
Change in SF-36 Quality of Life Physical Component Summary
Short Form (36) Health Survey The SF-36 evaluates health-related quality of life in 8 domains consisting of two components: physical and mental. The score for each domain ranges from 0 to 100. Norm based scoring (based on the general US population) is used with a mean of 50 and standard deviation of 10. Higher values represent a better outcome.
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in SF-36 Quality of Life Physical Component Summary | 0 units on a scale | Standard Deviation 7 |
| Placebo | Change in SF-36 Quality of Life Physical Component Summary | -1 units on a scale | Standard Deviation 7 |
p-value: 0.2295% CI: [-1, 3]ANCOVA
Secondary
Change in Systolic Blood Pressure
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Systolic Blood Pressure | -4 mm Hg | Standard Deviation 17 |
| Placebo | Change in Systolic Blood Pressure | -1 mm Hg | Standard Deviation 16 |
p-value: 0.0595% CI: [-7, 0]ANCOVA
Secondary
Change in Total Bilirubin
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Total Bilirubin | -1.0 μmol/L | Standard Deviation 4.1 |
| Placebo | Change in Total Bilirubin | 0.6 μmol/L | Standard Deviation 3.7 |
p-value: 0.00295% CI: [-2.4, -0.5]ANCOVA
Secondary
Change in Total Cholesterol
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Total Cholesterol | 0.16 mmol/L | Standard Deviation 1.07 |
| Placebo | Change in Total Cholesterol | -0.19 mmol/L | Standard Deviation 0.96 |
p-value: 0.000995% CI: [0.16, 0.6]ANCOVA
Secondary
Change in Total Protein
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Total Protein | 0.2 gl/L | Standard Deviation 4.5 |
| Placebo | Change in Total Protein | -0.5 gl/L | Standard Deviation 4.5 |
p-value: 0.3195% CI: [-0.5, 1.6]ANCOVA
Secondary
Change in Triglycerides
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Triglycerides | -0.22 mmol/L | Standard Deviation 1.27 |
| Placebo | Change in Triglycerides | -0.08 mmol/L | Standard Deviation 1.74 |
p-value: 0.8895% CI: [-0.35, 0.3]ANCOVA
Secondary
Change in Uric Acid
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Uric Acid | 2 μmol/L | Standard Deviation 68 |
| Placebo | Change in Uric Acid | -11 μmol/L | Standard Deviation 56 |
p-value: 0.0595% CI: [0, 29]ANCOVA
Secondary
Change in Waist Circumference
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Waist Circumference | -1.5 cm | Standard Deviation 7.1 |
| Placebo | Change in Waist Circumference | -0.6 cm | Standard Deviation 8.7 |
p-value: 0.795% CI: [-2.2, 1.5]ANCOVA
Secondary
Change in Waist-to-hip Ratio
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Waist-to-hip Ratio | 0.00 ratio | Standard Deviation 0.06 |
| Placebo | Change in Waist-to-hip Ratio | 0.00 ratio | Standard Deviation 0.06 |
p-value: 0.5795% CI: [-0.01, 0.02]ANCOVA
Secondary
Change in Weight
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in Weight | -2.3 kg | Standard Deviation 6.7 |
| Placebo | Change in Weight | 0.0 kg | Standard Deviation 6.1 |
p-value: 0.00895% CI: [-3.7, -0.6]ANCOVA
Secondary
Change in White Blood Cell Count
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in White Blood Cell Count | 0.0 white blood cells *10^9 per L | Standard Deviation 1.5 |
| Placebo | Change in White Blood Cell Count | 0.0 white blood cells *10^9 per L | Standard Deviation 1.1 |
p-value: 0.495% CI: [-0.2, 0.4]ANCOVA
Secondary
Change in γ-glutamyl Transpeptidase
Time frame: baseline to 72 weeks
Population: All patients who completed their final on-treatment study visit and the visit 24 weeks after stopping treatment (including those without a final biopsy due to early treatment termination) were included in the group comparisons of non-histological secondary outcomes.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Change in γ-glutamyl Transpeptidase | -37 U/L | Standard Deviation 70 |
| Placebo | Change in γ-glutamyl Transpeptidase | -6 U/L | Standard Deviation 48 |
p-value: <0.000195% CI: [-35, -14]ANCOVA
Secondary
Fibrosis: Change in Score
Change in fibrosis score. Fibrosis was assessed on a scale of 0-4, with higher scores showing more severe fibrosis.
Time frame: baseline to 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Fibrosis: Change in Score | -0.2 units on a scale | Standard Deviation 1 |
| Placebo | Fibrosis: Change in Score | 0.1 units on a scale | Standard Deviation 0.9 |
p-value: 0.0195% CI: [-0.6, -0.1]ANCOVA
Secondary
Fibrosis: Patient With Improvement
Patients with improvement in fibrosis score. Fibrosis was assessed on a scale of 0-4, with higher scores showing more severe fibrosis.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Fibrosis: Patient With Improvement | 36 participants |
| Placebo | Fibrosis: Patient With Improvement | 19 participants |
p-value: 0.00495% CI: [1.1, 2.7]Cochran-Mantel-Haenszel
Secondary
Hepatocellular Ballooning: Change in Score
Change in hepatocellular ballooning score. Hepatocellular ballooning was assessed on a scale of 0-2, with higher scores showing more severe ballooning.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Hepatocellular Ballooning: Change in Score | -0.5 units on a scale | Standard Deviation 0.9 |
| Placebo | Hepatocellular Ballooning: Change in Score | -0.2 units on a scale | Standard Deviation 0.9 |
p-value: 0.0395% CI: [-0.5, 0]ANCOVA
Secondary
Hepatocellular Ballooning: Patients With Improvement
Patients with improvement in hepatocellular ballooning score. Hepatocellular ballooning was assessed on a scale of 0-2, with higher scores showing more severe ballooning.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Hepatocellular Ballooning: Patients With Improvement | 47 participants |
| Placebo | Hepatocellular Ballooning: Patients With Improvement | 30 participants |
p-value: 0.0395% CI: [1, 2.1]Cochran-Mantel-Haenszel
Secondary
Lobular Inflammation: Change in Score
Change in lobular inflammation score. Lobular inflammation was assessed on a scale of 0-3, with higher scores showing more severe lobular inflammation.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Lobular Inflammation: Change in Score | -0.5 units on a scale | Standard Deviation 0.8 |
| Placebo | Lobular Inflammation: Change in Score | -0.2 units on a scale | Standard Deviation 0.9 |
p-value: 0.000695% CI: [-0.5, -0.1]ANCOVA
Secondary
Lobular Inflammation: Patients With Improvement
Patients with improvement in lobular inflammation score. Lobular inflammation was assessed on a scale of 0-3, with higher scores showing more severe lobular inflammation.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Lobular Inflammation: Patients With Improvement | 54 participants |
| Placebo | Lobular Inflammation: Patients With Improvement | 34 participants |
p-value: 0.00695% CI: [1.1, 2.2]Cochran-Mantel-Haenszel
Secondary
Portal Inflammation: Change in Score
Change in portal inflammation score. Portal inflammation was assessed on a scale of 0-3, with higher scores showing more severe portal inflammation.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Portal Inflammation: Change in Score | 0.2 units on a scale | Standard Deviation 0.7 |
| Placebo | Portal Inflammation: Change in Score | 0.2 units on a scale | Standard Deviation 0.7 |
p-value: 0.5995% CI: [-0.1, 0.2]ANCOVA
Secondary
Portal Inflammation: Patients With Improvement
Patients with improvement in portal inflammation score. Portal inflammation was assessed on a scale of 0-2, with higher scores showing more severe portal inflammation.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Portal Inflammation: Patients With Improvement | 12 participants |
| Placebo | Portal Inflammation: Patients With Improvement | 13 participants |
p-value: 0.995% CI: [0.6, 1.7]Cochran-Mantel-Haenszel
Secondary
Resolution of NASH Diagnosis
Resolution of definite nonalcoholic steatohepatitis. Resolution defined as either not NAFLD, or NAFLD but not non-alcoholic steatohepatitis on week 72 biopsy
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Resolution of NASH Diagnosis | 22 participants |
| Placebo | Resolution of NASH Diagnosis | 13 participants |
p-value: 0.0895% CI: [0.9, 2.6]Cochran-Mantel-Haenszel
Secondary
Steatosis: Change in Score
Change in steatosis score. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Steatosis: Change in Score | -0.8 units on a scale | Standard Deviation 1 |
| Placebo | Steatosis: Change in Score | -0.4 units on a scale | Standard Deviation 0.8 |
p-value: 0.000495% CI: [-0.6, -0.2]ANCOVA
Secondary
Steatosis: Patients With Improvement
Patients with improvement in steatosis score. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis.
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeticholic Acid | Steatosis: Patients With Improvement | 62 participants |
| Placebo | Steatosis: Patients With Improvement | 37 participants |
p-value: 0.00195% CI: [1.2, 2.3]Cochran-Mantel-Haenszel
Secondary
Total NAFLD Activity Score: Change in Score
NAFLD activity score was assessed on a scale of 0-8, with higher scores showing more severe disease (the components of this measure are steatosis \[assessed on a scale of 0-3\], lobular inflammation \[assessed on a scale of 0-3\], and hepatocellular ballooning \[assessed on a scale of 0-2\]).
Time frame: baseline to 72 weeks
Population: Number of patients with biopsy specimens at baseline and 72 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid | Total NAFLD Activity Score: Change in Score | -1.7 units on a scale | Standard Deviation 1.8 |
| Placebo | Total NAFLD Activity Score: Change in Score | -0.7 units on a scale | Standard Deviation 1.8 |
p-value: <0.000195% CI: [-1.3, -0.5]ANCOVA