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The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in NASH Treatment Trial(FLINT) (FLINT)

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ClinicalTrials.gov Identifier: NCT01265498
Recruitment Status : Completed
First Posted : December 23, 2010
Results First Posted : August 21, 2015
Last Update Posted : April 6, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic Steatohepatitis (NASH)
Interventions Drug: obeticholic acid
Drug: placebo
Enrollment 283

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Period Title: Overall Study
Started 141 142
Both Baseline and Week 72 Biopsy 102 98
Completed 110 109
Not Completed 31 33
Reason Not Completed
Protocol modified to eliminate wk72 bx             31             33
Arm/Group Title Obeticholic Acid Placebo Total
Hide Arm/Group Description

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Total of all reporting groups
Overall Number of Baseline Participants 141 142 283
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 141 participants 142 participants 283 participants
52  (11) 51  (12) 51  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
Female
98
  69.5%
89
  62.7%
187
  66.1%
Male
43
  30.5%
53
  37.3%
96
  33.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
Hispanic or Latino
22
  15.6%
21
  14.8%
43
  15.2%
Not Hispanic or Latino
119
  84.4%
121
  85.2%
240
  84.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
Asian 6 10 16
Black or African-American 2 4 6
White 123 111 234
Other 10 17 27
SF-36 Quality of life: Physical component summary   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
45  (11) 44  (11) 44  (11)
[1]
Measure Description: 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.
SF-36 Quality of life: Mental component summary   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
48  (12) 48  (12) 48  (12)
[1]
Measure Description: 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.
Liver enzymes: Alanine aminotransferase  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 141 participants 142 participants 283 participants
83  (49) 82  (51) 83  (50)
Liver enzymes: Aspartate aminotransferase  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 141 participants 142 participants 283 participants
64  (38) 58  (34) 61  (36)
Liver enzymes: Alkaline phosphatase  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 141 participants 142 participants 283 participants
82  (29) 81  (25) 82  (27)
Liver enzymes: γ-glutamyl transpeptidase  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 141 participants 142 participants 283 participants
78  (85) 76  (97) 77  (91)
Liver enzymes: Total bilirubin  
Mean (Standard Deviation)
Unit of measure:  μmol/L
Number Analyzed 141 participants 142 participants 283 participants
11.5  (5.9) 11.3  (7.5) 11.4  (6.8)
Lipids: Total cholesterol  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
4.9  (1.2) 4.8  (1.2) 4.9  (1.2)
Lipids: HDL cholesterol  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
1.1  (0.3) 1.1  (0.4) 1.1  (0.3)
Lipids: LDL cholesterol  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
2.9  (1.0) 2.9  (1.1) 2.9  (1.0)
Lipids: Triglycerides  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
2.2  (1.5) 2.0  (1.7) 2.1  (1.6)
Haematology: Haemoglobin  
Mean (Standard Deviation)
Unit of measure:  g/L
Number Analyzed 141 participants 142 participants 283 participants
140  (15) 140  (14) 140  (14)
Haematology: Haematocrit  
Mean (Standard Deviation)
Unit of measure:  Proportion of 1·0
Number Analyzed 141 participants 142 participants 283 participants
0.41  (0.04) 0.41  (0.04) 0.41  (0.04)
Haematology: Mean corpuscular volume  
Mean (Standard Deviation)
Unit of measure:  fL
Number Analyzed 141 participants 142 participants 283 participants
88.7  (4.8) 89.0  (5.3) 88.9  (5.1)
Haematology: White blood cell count  
Mean (Standard Deviation)
Unit of measure:  White blood cells *10^9 per L
Number Analyzed 141 participants 142 participants 283 participants
7.3  (1.9) 6.9  (2.3) 7.1  (2.1)
Haematology: Platelet count  
Mean (Standard Deviation)
Unit of measure:  Platelets *10^9 per L
Number Analyzed 141 participants 142 participants 283 participants
237  (59) 237  (65) 237  (62)
Chemistries: Bicarbonate  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
25.9  (2.5) 26.2  (2.6) 26.0  (2.5)
Chemistries: Calcium  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
2.4  (0.1) 2.4  (0.1) 2.4  (0.1)
Chemistries: Phosphate  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
1.1  (0.2) 1.1  (0.2) 1.1  (0.2)
Chemistries: Creatinine  
Mean (Standard Deviation)
Unit of measure:  μmol/L
Number Analyzed 141 participants 142 participants 283 participants
71  (18) 70  (16) 71  (17)
Chemistries: Uric acid  
Mean (Standard Deviation)
Unit of measure:  μmol/L
Number Analyzed 141 participants 142 participants 283 participants
375  (89) 366  (86) 370  (87)
Chemistries: Albumin  
Mean (Standard Deviation)
Unit of measure:  g/L
Number Analyzed 141 participants 142 participants 283 participants
43  (4) 43  (4) 43  (4)
Chemistries: Total protein  
Mean (Standard Deviation)
Unit of measure:  g/L
Number Analyzed 141 participants 142 participants 283 participants
73  (5) 74  (5) 73  (5)
Other laboratory results: Prothrombin time  
Mean (Standard Deviation)
Unit of measure:  s
Number Analyzed 141 participants 142 participants 283 participants
11.7  (2.1) 11.7  (2.2) 11.7  (2.1)
Other laboratory results: International normalised ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 141 participants 142 participants 283 participants
1.01  (0.08) 1.00  (0.07) 1.00  (0.07)
Metabolic factors: Fasting serum glucose  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 141 participants 142 participants 283 participants
6.5  (1.8) 6.4  (2.2) 6.4  (2.0)
Metabolic factors: Insulin  
Mean (Standard Deviation)
Unit of measure:  pmol/L
Number Analyzed 141 participants 142 participants 283 participants
201  (226) 138  (129) 169  (186)
Metabolic factors: HOMA-IR  
Mean (Standard Deviation)
Unit of measure:  Glucose [mmol/L] × insulin [pmol/L]/22.5
Number Analyzed 141 participants 142 participants 283 participants
61  (74) 40  (42) 50  (61)
Metabolic factors: Glycated haemoglobin A1c  
Mean (Standard Deviation)
Unit of measure:  Mmol/mol
Number Analyzed 141 participants 142 participants 283 participants
48  (12) 47  (11) 47  (11)
Metabolic factors: Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 141 participants 142 participants 283 participants
100  (23) 96  (18) 98  (21)
Metabolic factors: Body-mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m²
Number Analyzed 141 participants 142 participants 283 participants
35  (7) 34  (6) 35  (6)
Metabolic factors: Waist circumference  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 141 participants 142 participants 283 participants
112  (15) 109  (14) 111  (15)
Metabolic factors: Waist-to-hip ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 141 participants 142 participants 283 participants
0.96  (0.07) 0.95  (0.09) 0.95  (0.08)
Metabolic factors: Systolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 141 participants 142 participants 283 participants
132  (17) 132  (15) 132  (16)
Metabolic factors: Diastolic blood pressure  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 141 participants 142 participants 283 participants
77  (11) 78  (10) 77  (10)
Comorbidities: Hyperlipidaemia   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
87 86 173
[1]
Measure Description: History of cholesterol or triglyceride elevations as determined by the site investigator.
Comorbidities: Hypertension  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
87 85 172
Comorbidities: Cardiovascular disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
7 8 15
Comorbidities: Diabetes  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
75 74 149
Concomitant medications in the past 6 months: Antilipidaemic  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
72 64 136
Concomitant medications in the past 6 months: Cardiovascular  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
97 92 189
Concomitant medications in the past 6 months: Antidiabetic  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
67 73 140
Concomitant medications in the past 6 months: Metformin  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
55 62 117
Concomitant medications in the past 6 months: Pioglitazone  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
1 6 7
Concomitant medications in the past 6 months: Vitamin E  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
29 32 61
Concomitant medications in the past 6 months: Thiazolidinedione  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
3 5 8
Concomitant medications in the past 6 months: Aspirin (81 mg)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
37 33 70
Liver histology findings: Definite steatohepatitis  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 142 participants 283 participants
114 111 225
Liver histology findings: Fibrosis stage   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
1.9  (1.1) 1.8  (1.0) 1.8  (1.1)
[1]
Measure Description: †Fibrosis was assessed on a scale of 0–4, with higher scores showing more severe fibrosis.
Liver histology findings: Total NAFLD activity score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
5.3  (1.3) 5.1  (1.3) 5.2  (1.3)
[1]
Measure Description: Total non-alcoholic fatty liver disease (NAFLD) activity was assessed on a scale of 0–8, with higher scores indicating 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).
Liver histology findings: Hepatocellular ballooning score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
1.4  (0.7) 1.3  (0.7) 1.4  (0.7)
[1]
Measure Description: Assessed on a scale of 0–2 with higher scores showing more severe ballooning.
Liver histology findings: Steatosis score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
2.1  (0.8) 2.0  (0.8) 2.0  (0.8)
[1]
Measure Description: Assessed on a scale of 0–3 with higher scores showing more severe steatosis.
Liver histology findings: Lobular inflammation score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
1.8  (0.7) 1.8  (0.7) 1.8  (0.7)
[1]
Measure Description: Assessed on a scale of 0–3 with higher scores showing more severe lobular inflammation.
Liver histology findings: Portal inflammation score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 141 participants 142 participants 283 participants
1.2  (0.6) 1.1  (0.6) 1.1  (0.6)
[1]
Measure Description: Portal inflammation was assessed on a scale of 0–2 with higher scores showing more severe inflammation.
Liver histology findings: Biopsy length  
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 141 participants 142 participants 283 participants
21  (10) 21  (10) 21  (10)
1.Primary Outcome
Title Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 110 109
Measure Type: Number
Unit of Measure: participants
50 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
1.3 to 2.8
Estimation Comments obeticholic acid vs placebo
2.Secondary Outcome
Title Resolution of NASH Diagnosis
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: participants
22 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
0.9 to 2.6
Estimation Comments obeticholic acid vs placebo
3.Secondary Outcome
Title Fibrosis: Patient With Improvement
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: participants
36 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
1.1 to 2.7
Estimation Comments obeticholic acid vs placebo
4.Secondary Outcome
Title Fibrosis: Change in Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.2  (1.0) 0.1  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.6 to -0.1
Estimation Comments obeticholic acid vs placebo
5.Secondary Outcome
Title Total NAFLD Activity Score: Change in Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.7  (1.8) -0.7  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.3 to -0.5
Estimation Comments obeticholic acid vs placebo
6.Secondary Outcome
Title Hepatocellular Ballooning: Patients With Improvement
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: participants
47 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
1.0 to 2.1
Estimation Comments obeticholic acid vs placebo
7.Secondary Outcome
Title Hepatocellular Ballooning: Change in Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.5  (0.9) -0.2  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.0
Estimation Comments obeticholic acid vs placebo
8.Secondary Outcome
Title Steatosis: Patients With Improvement
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: participants
62 37
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
1.2 to 2.3
Estimation Comments obeticholic acid vs. placebo
9.Secondary Outcome
Title Steatosis: Change in Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.8  (1.0) -0.4  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.6 to -0.2
Estimation Comments obeticholic acid vs placebo
10.Secondary Outcome
Title Lobular Inflammation: Patients With Improvement
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: participants
54 34
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
1.1 to 2.2
Estimation Comments obeticholic acid vs. placebo
11.Secondary Outcome
Title Lobular Inflammation: Change in Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.5  (0.8) -0.2  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.5 to -0.1
Estimation Comments obeticholic acid vs placebo
12.Secondary Outcome
Title Portal Inflammation: Patients With Improvement
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Measure Type: Number
Unit of Measure: participants
12 13
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.90
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments p values and relative benefit were calculated with the Cochran-Mantel-Haenszel chi-square test, stratified by clinic and diabetes status
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.6 to 1.7
Estimation Comments obeticholic acid vs. placebo
13.Secondary Outcome
Title Portal Inflammation: Change in Score
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients with biopsy specimens at baseline and 72 weeks
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 102 98
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.2  (0.7) 0.2  (0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.1 to 0.2
Estimation Comments obeticholic acid vs placebo
14.Secondary Outcome
Title Change in Alanine Aminotransferase
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: U/L
-38  (47) -18  (44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -20
Confidence Interval (2-Sided) 95%
-28 to -11
Estimation Comments obeticholic acid vs placebo
15.Secondary Outcome
Title Change in Asparate Aminotransferase
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: U/L
-27  (37) -10  (31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -12
Confidence Interval (2-Sided) 95%
-18 to -6
Estimation Comments obeticholic acid vs placebo
16.Secondary Outcome
Title Change in Alkaline Phosphatase
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: U/L
12  (26) -6  (20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 18
Confidence Interval (2-Sided) 95%
13 to 24
Estimation Comments obeticholic acid vs placebo
17.Secondary Outcome
Title Change in γ-glutamyl Transpeptidase
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: U/L
-37  (70) -6  (48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -24
Confidence Interval (2-Sided) 95%
-35 to -14
Estimation Comments obeticholic acid vs placebo
18.Secondary Outcome
Title Change in Total Bilirubin
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: μmol/L
-1.0  (4.1) 0.6  (3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.4 to -0.5
Estimation Comments obeticholic acid vs placebo
19.Secondary Outcome
Title Change in Total Cholesterol
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.16  (1.07) -0.19  (0.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.16 to 0.60
Estimation Comments obeticholic acid vs placebo
20.Secondary Outcome
Title Change in HDL Cholesterol
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.02  (0.20) 0.03  (0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.10 to -0.01
Estimation Comments obeticholic acid vs placebo
21.Secondary Outcome
Title Change in LDL Cholesterol
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.22  (0.90) -0.22  (0.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.26 to 0.65
Estimation Comments obeticholic acid vs placebo
22.Secondary Outcome
Title Change in Triglycerides
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.22  (1.27) -0.08  (1.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.35 to 0.30
Estimation Comments obeticholic acid vs placebo
23.Secondary Outcome
Title Change in Haemoglobin
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: g/L
0.6  (9.6) 0.3  (9.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.8 to 2.6
Estimation Comments obeticholic acid vs placebo
24.Secondary Outcome
Title Change in Haematocrit
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: proportion of 1.0
0.00  (0.03) 0.00  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.01 to 0.01
Estimation Comments obeticholic acid vs placebo
25.Secondary Outcome
Title Change in Mean Corpuscular Volume
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: fL
-0.8  (2.6) 0.3  (3.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-1.8 to -0.4
Estimation Comments obeticholic acid vs placebo
26.Secondary Outcome
Title Change in White Blood Cell Count
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: white blood cells *10^9 per L
0.0  (1.5) 0.0  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.4
Estimation Comments obeticholic acid vs placebo
27.Secondary Outcome
Title Change in Platelet Count
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: platelets *10^9 per L
12  (33) -4  (46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 16
Confidence Interval (2-Sided) 95%
7 to 26
Estimation Comments obeticholic acid vs placebo
28.Secondary Outcome
Title Change in Bicarbonate
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.7  (3.2) -0.1  (2.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.4 to -0.1
Estimation Comments obeticholic acid vs placebo
29.Secondary Outcome
Title Change in Calcium
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.01  (0.10) -0.01  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
0.00 to 0.04
Estimation Comments obeticholic acid vs placebo
30.Secondary Outcome
Title Change in Phosphate
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.01  (0.18) 0.02  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.05
Estimation Comments obeticholic acid vs placebo
31.Secondary Outcome
Title Change in Creatinine
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: μmol/L
1.5  (11.3) -1.1  (9.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
0.2 to 5.0
Estimation Comments obeticholic acid vs placebo
32.Secondary Outcome
Title Change in Uric Acid
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: μmol/L
2  (68) -11  (56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 14
Confidence Interval (2-Sided) 95%
0 to 29
Estimation Comments obeticholic acid vs placebo
33.Secondary Outcome
Title Change in Albumin
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: gl/L
-0.2  (3.1) 0.3  (3.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.2 to 0.2
Estimation Comments obeticholic acid vs placebo
34.Secondary Outcome
Title Change in Total Protein
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: gl/L
0.2  (4.5) -0.5  (4.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.5 to 1.6
Estimation Comments obeticholic acid vs placebo
35.Secondary Outcome
Title Change in Prothrombin Time
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: s
-0.1  (2.4) 0.0  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.6 to 0.1
Estimation Comments obeticholic acid vs placebo
36.Secondary Outcome
Title Change in International Normalised Ratio
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: ratio
-0.03  (0.07) 0.00  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.04 to -0.01
Estimation Comments obeticholic acid vs placebo
37.Secondary Outcome
Title Change in Fasting Serum Glucose
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.4  (2.1) 0.2  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.2 to 0.8
Estimation Comments obeticholic acid vs placebo
38.Secondary Outcome
Title Change in Insulin
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: pmol/L
29  (159) 10  (111)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 38
Confidence Interval (2-Sided) 95%
6 to 69
Estimation Comments obeticholic acid vs placebo
39.Secondary Outcome
Title Change in HOMA-IR
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: glucose[mmol/L]× insulin[pmol/L] / 22.5
15  (50) 4  (29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13
Confidence Interval (2-Sided) 95%
3 to 23
Estimation Comments obeticholic acid vs placebo
40.Secondary Outcome
Title Change in Glycated Haemoglobin A1c
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mmol/mol
0.5  (9.7) 0.4  (8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.7 to 2.6
Estimation Comments obeticholic acid vs placebo
41.Secondary Outcome
Title Change in Weight
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: kg
-2.3  (6.7) 0.0  (6.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-3.7 to -0.6
Estimation Comments obeticholic acid vs placebo
42.Secondary Outcome
Title Change in Body-mass Index
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: kg/m²
-0.7  (2.4) 0.1  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.3 to -0.2
Estimation Comments obeticholic acid vs placebo
43.Secondary Outcome
Title Change in Waist Circumference
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: cm
-1.5  (7.1) -0.6  (8.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-2.2 to 1.5
Estimation Comments obeticholic acid vs placebo
44.Secondary Outcome
Title Change in Waist-to-hip Ratio
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: ratio
0.00  (0.06) 0.00  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.01 to 0.02
Estimation Comments obeticholic acid vs placebo
45.Secondary Outcome
Title Change in Systolic Blood Pressure
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mm Hg
-4  (17) -1  (16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3
Confidence Interval (2-Sided) 95%
-7 to 0
Estimation Comments obeticholic acid vs placebo
46.Secondary Outcome
Title Change in Diastolic Blood Pressure
Hide Description [Not Specified]
Time Frame baseline to 72 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: mm Hg
0  (11) 0  (10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1
Confidence Interval (2-Sided) 95%
-4 to 1
Estimation Comments obeticholic acid vs placebo
47.Secondary Outcome
Title Change in SF-36 Quality of Life Physical Component Summary
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: units on a scale
0  (7) -1  (7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1
Confidence Interval (2-Sided) 95%
-1 to 3
Estimation Comments obeticholic acid vs placebo
48.Secondary Outcome
Title Change in SF-36 Quality of Life Mental Component Summary
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description:

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Overall Number of Participants Analyzed 126 131
Mean (Standard Deviation)
Unit of Measure: units on a scale
0  (9) 1  (9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Obeticholic Acid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method ANCOVA
Comments calculated using ANCOVA models, regressing change from baseline to 72 weeks on treatment group and baseline value of the outcome
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3 to 2
Estimation Comments obeticholic acid vs placebo
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Obeticholic Acid Placebo
Hide Arm/Group Description

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

All-Cause Mortality
Obeticholic Acid Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Obeticholic Acid Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/141 (9.22%)      10/142 (7.04%)    
Cardiac disorders     
Cardiovascular death or non-fatal myocardial infarction or non-fatal stroke * 1  3/141 (2.13%)  3 1/142 (0.70%)  2
Other coronary artery disease or angina * 1  2/141 (1.42%)  2 2/142 (1.41%)  2
Other cardiovascular event * 1  1/141 (0.71%)  1 1/142 (0.70%)  1
Gastrointestinal disorders     
Abdominal pain * 1  0/141 (0.00%)  0 2/142 (1.41%)  2
Pancreatitis * 1  1/141 (0.71%)  1 1/142 (0.70%)  1
Other gastrointestinal event * 1  2/141 (1.42%)  2 0/142 (0.00%)  0
Hepatobiliary disorders     
Hepatobiliary events * 1  1/141 (0.71%)  1 1/142 (0.70%)  1
Nervous system disorders     
Other neurological event * 1  1/141 (0.71%)  1 2/142 (1.41%)  2
Renal and urinary disorders     
Other renal event * 1  1/141 (0.71%)  1 0/142 (0.00%)  0
Skin and subcutaneous tissue disorders     
Pruritis * 1  1/141 (0.71%)  1 0/142 (0.00%)  0