ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Obeticholic Acid

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks


Participant Flow:   Overall Study
    Obeticholic Acid   Placebo
STARTED   141   142 
Both Baseline and Week 72 Biopsy   102   98 
COMPLETED   110   109 
NOT COMPLETED   31   33 
Protocol modified to eliminate wk72 bx                31                33 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Obeticholic Acid

obeticholic acid

obeticholic acid: 25 mg daily for 72 weeks

Placebo

Placebo

placebo: placebo capsule, 25 mg daily for 72 weeks

Total Total of all reporting groups

Baseline Measures
   Obeticholic Acid   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 141   142   283 
Age 
[Units: Years]
Mean (Standard Deviation)
 52  (11)   51  (12)   51  (11) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      98  69.5%      89  62.7%      187  66.1% 
Male      43  30.5%      53  37.3%      96  33.9% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of 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 
[Units: 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] 
[Units: Units on a scale]
Mean (Standard Deviation)
 45  (11)   44  (11)   44  (11) 
[1] 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] 
[Units: Units on a scale]
Mean (Standard Deviation)
 48  (12)   48  (12)   48  (12) 
[1] 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 
[Units: U/L]
Mean (Standard Deviation)
 83  (49)   82  (51)   83  (50) 
Liver enzymes: Aspartate aminotransferase 
[Units: U/L]
Mean (Standard Deviation)
 64  (38)   58  (34)   61  (36) 
Liver enzymes: Alkaline phosphatase 
[Units: U/L]
Mean (Standard Deviation)
 82  (29)   81  (25)   82  (27) 
Liver enzymes: γ-glutamyl transpeptidase 
[Units: U/L]
Mean (Standard Deviation)
 78  (85)   76  (97)   77  (91) 
Liver enzymes: Total bilirubin 
[Units: μmol/L]
Mean (Standard Deviation)
 11.5  (5.9)   11.3  (7.5)   11.4  (6.8) 
Lipids: Total cholesterol 
[Units: mmol/L]
Mean (Standard Deviation)
 4.9  (1.2)   4.8  (1.2)   4.9  (1.2) 
Lipids: HDL cholesterol 
[Units: mmol/L]
Mean (Standard Deviation)
 1.1  (0.3)   1.1  (0.4)   1.1  (0.3) 
Lipids: LDL cholesterol 
[Units: mmol/L]
Mean (Standard Deviation)
 2.9  (1.0)   2.9  (1.1)   2.9  (1.0) 
Lipids: Triglycerides 
[Units: mmol/L]
Mean (Standard Deviation)
 2.2  (1.5)   2.0  (1.7)   2.1  (1.6) 
Haematology: Haemoglobin 
[Units: g/L]
Mean (Standard Deviation)
 140  (15)   140  (14)   140  (14) 
Haematology: Haematocrit 
[Units: Proportion of 1·0]
Mean (Standard Deviation)
 0.41  (0.04)   0.41  (0.04)   0.41  (0.04) 
Haematology: Mean corpuscular volume 
[Units: fL]
Mean (Standard Deviation)
 88.7  (4.8)   89.0  (5.3)   88.9  (5.1) 
Haematology: White blood cell count 
[Units: White blood cells *10^9 per L]
Mean (Standard Deviation)
 7.3  (1.9)   6.9  (2.3)   7.1  (2.1) 
Haematology: Platelet count 
[Units: Platelets *10^9 per L]
Mean (Standard Deviation)
 237  (59)   237  (65)   237  (62) 
Chemistries: Bicarbonate 
[Units: mmol/L]
Mean (Standard Deviation)
 25.9  (2.5)   26.2  (2.6)   26.0  (2.5) 
Chemistries: Calcium 
[Units: mmol/L]
Mean (Standard Deviation)
 2.4  (0.1)   2.4  (0.1)   2.4  (0.1) 
Chemistries: Phosphate 
[Units: mmol/L]
Mean (Standard Deviation)
 1.1  (0.2)   1.1  (0.2)   1.1  (0.2) 
Chemistries: Creatinine 
[Units: μmol/L]
Mean (Standard Deviation)
 71  (18)   70  (16)   71  (17) 
Chemistries: Uric acid 
[Units: μmol/L]
Mean (Standard Deviation)
 375  (89)   366  (86)   370  (87) 
Chemistries: Albumin 
[Units: g/L]
Mean (Standard Deviation)
 43  (4)   43  (4)   43  (4) 
Chemistries: Total protein 
[Units: g/L]
Mean (Standard Deviation)
 73  (5)   74  (5)   73  (5) 
Other laboratory results: Prothrombin time 
[Units: s]
Mean (Standard Deviation)
 11.7  (2.1)   11.7  (2.2)   11.7  (2.1) 
Other laboratory results: International normalised ratio 
[Units: Ratio]
Mean (Standard Deviation)
 1.01  (0.08)   1.00  (0.07)   1.00  (0.07) 
Metabolic factors: Fasting serum glucose 
[Units: mmol/L]
Mean (Standard Deviation)
 6.5  (1.8)   6.4  (2.2)   6.4  (2.0) 
Metabolic factors: Insulin 
[Units: pmol/L]
Mean (Standard Deviation)
 201  (226)   138  (129)   169  (186) 
Metabolic factors: HOMA-IR 
[Units: Glucose [mmol/L] × insulin [pmol/L]/22.5]
Mean (Standard Deviation)
 61  (74)   40  (42)   50  (61) 
Metabolic factors: Glycated haemoglobin A1c 
[Units: Mmol/mol]
Mean (Standard Deviation)
 48  (12)   47  (11)   47  (11) 
Metabolic factors: Weight 
[Units: Kg]
Mean (Standard Deviation)
 100  (23)   96  (18)   98  (21) 
Metabolic factors: Body-mass index 
[Units: Kg/m²]
Mean (Standard Deviation)
 35  (7)   34  (6)   35  (6) 
Metabolic factors: Waist circumference 
[Units: Cm]
Mean (Standard Deviation)
 112  (15)   109  (14)   111  (15) 
Metabolic factors: Waist-to-hip ratio 
[Units: Ratio]
Mean (Standard Deviation)
 0.96  (0.07)   0.95  (0.09)   0.95  (0.08) 
Metabolic factors: Systolic blood pressure 
[Units: Mm Hg]
Mean (Standard Deviation)
 132  (17)   132  (15)   132  (16) 
Metabolic factors: Diastolic blood pressure 
[Units: Mm Hg]
Mean (Standard Deviation)
 77  (11)   78  (10)   77  (10) 
Comorbidities: Hyperlipidaemia [1] 
[Units: Participants]
 87   86   173 
[1] History of cholesterol or triglyceride elevations as determined by the site investigator.
Comorbidities: Hypertension 
[Units: Participants]
 87   85   172 
Comorbidities: Cardiovascular disease 
[Units: Participants]
 7   8   15 
Comorbidities: Diabetes 
[Units: Participants]
 75   74   149 
Concomitant medications in the past 6 months: Antilipidaemic 
[Units: Participants]
 72   64   136 
Concomitant medications in the past 6 months: Cardiovascular 
[Units: Participants]
 97   92   189 
Concomitant medications in the past 6 months: Antidiabetic 
[Units: Participants]
 67   73   140 
Concomitant medications in the past 6 months: Metformin 
[Units: Participants]
 55   62   117 
Concomitant medications in the past 6 months: Pioglitazone 
[Units: Participants]
 1   6   7 
Concomitant medications in the past 6 months: Vitamin E 
[Units: Participants]
 29   32   61 
Concomitant medications in the past 6 months: Thiazolidinedione 
[Units: Participants]
 3   5   8 
Concomitant medications in the past 6 months: Aspirin (81 mg) 
[Units: Participants]
 37   33   70 
Liver histology findings: Definite steatohepatitis 
[Units: Participants]
 114   111   225 
Liver histology findings: Fibrosis stage [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.9  (1.1)   1.8  (1.0)   1.8  (1.1) 
[1] †Fibrosis was assessed on a scale of 0–4, with higher scores showing more severe fibrosis.
Liver histology findings: Total NAFLD activity score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 5.3  (1.3)   5.1  (1.3)   5.2  (1.3) 
[1] 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] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.4  (0.7)   1.3  (0.7)   1.4  (0.7) 
[1] Assessed on a scale of 0–2 with higher scores showing more severe ballooning.
Liver histology findings: Steatosis score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.1  (0.8)   2.0  (0.8)   2.0  (0.8) 
[1] Assessed on a scale of 0–3 with higher scores showing more severe steatosis.
Liver histology findings: Lobular inflammation score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.8  (0.7)   1.8  (0.7)   1.8  (0.7) 
[1] Assessed on a scale of 0–3 with higher scores showing more severe lobular inflammation.
Liver histology findings: Portal inflammation score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 1.2  (0.6)   1.1  (0.6)   1.1  (0.6) 
[1] Portal inflammation was assessed on a scale of 0–2 with higher scores showing more severe inflammation.
Liver histology findings: Biopsy length 
[Units: Mm]
Mean (Standard Deviation)
 21  (10)   21  (10)   21  (10) 


  Outcome Measures

1.  Primary:   Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)   [ Time Frame: baseline to 72 weeks ]

2.  Secondary:   Resolution of NASH Diagnosis   [ Time Frame: baseline to 72 weeks ]

3.  Secondary:   Fibrosis: Patient With Improvement   [ Time Frame: baseline to 72 weeks ]

4.  Secondary:   Fibrosis: Change in Score   [ Time Frame: baseline to 72 weeks ]

5.  Secondary:   Total NAFLD Activity Score: Change in Score   [ Time Frame: baseline to 72 weeks ]

6.  Secondary:   Hepatocellular Ballooning: Patients With Improvement   [ Time Frame: baseline to 72 weeks ]

7.  Secondary:   Hepatocellular Ballooning: Change in Score   [ Time Frame: baseline to 72 weeks ]

8.  Secondary:   Steatosis: Patients With Improvement   [ Time Frame: baseline to 72 weeks ]

9.  Secondary:   Steatosis: Change in Score   [ Time Frame: baseline to 72 weeks ]

10.  Secondary:   Lobular Inflammation: Patients With Improvement   [ Time Frame: baseline to 72 weeks ]

11.  Secondary:   Lobular Inflammation: Change in Score   [ Time Frame: baseline to 72 weeks ]

12.  Secondary:   Portal Inflammation: Patients With Improvement   [ Time Frame: baseline to 72 weeks ]

13.  Secondary:   Portal Inflammation: Change in Score   [ Time Frame: baseline to 72 weeks ]

14.  Secondary:   Change in Alanine Aminotransferase   [ Time Frame: baseline to 72 weeks ]

15.  Secondary:   Change in Asparate Aminotransferase   [ Time Frame: baseline to 72 weeks ]

16.  Secondary:   Change in Alkaline Phosphatase   [ Time Frame: baseline to 72 weeks ]

17.  Secondary:   Change in γ-glutamyl Transpeptidase   [ Time Frame: baseline to 72 weeks ]

18.  Secondary:   Change in Total Bilirubin   [ Time Frame: baseline to 72 weeks ]

19.  Secondary:   Change in Total Cholesterol   [ Time Frame: baseline to 72 weeks ]

20.  Secondary:   Change in HDL Cholesterol   [ Time Frame: baseline to 72 weeks ]

21.  Secondary:   Change in LDL Cholesterol   [ Time Frame: baseline to 72 weeks ]

22.  Secondary:   Change in Triglycerides   [ Time Frame: baseline to 72 weeks ]

23.  Secondary:   Change in Haemoglobin   [ Time Frame: baseline to 72 weeks ]

24.  Secondary:   Change in Haematocrit   [ Time Frame: baseline to 72 weeks ]

25.  Secondary:   Change in Mean Corpuscular Volume   [ Time Frame: baseline to 72 weeks ]

26.  Secondary:   Change in White Blood Cell Count   [ Time Frame: baseline to 72 weeks ]

27.  Secondary:   Change in Platelet Count   [ Time Frame: baseline to 72 weeks ]

28.  Secondary:   Change in Bicarbonate   [ Time Frame: baseline to 72 weeks ]

29.  Secondary:   Change in Calcium   [ Time Frame: baseline to 72 weeks ]

30.  Secondary:   Change in Phosphate   [ Time Frame: baseline to 72 weeks ]

31.  Secondary:   Change in Creatinine   [ Time Frame: baseline to 72 weeks ]

32.  Secondary:   Change in Uric Acid   [ Time Frame: baseline to 72 weeks ]

33.  Secondary:   Change in Albumin   [ Time Frame: baseline to 72 weeks ]

34.  Secondary:   Change in Total Protein   [ Time Frame: baseline to 72 weeks ]

35.  Secondary:   Change in Prothrombin Time   [ Time Frame: baseline to 72 weeks ]

36.  Secondary:   Change in International Normalised Ratio   [ Time Frame: baseline to 72 weeks ]

37.  Secondary:   Change in Fasting Serum Glucose   [ Time Frame: baseline to 72 weeks ]

38.  Secondary:   Change in Insulin   [ Time Frame: baseline to 72 weeks ]

39.  Secondary:   Change in HOMA-IR   [ Time Frame: baseline to 72 weeks ]

40.  Secondary:   Change in Glycated Haemoglobin A1c   [ Time Frame: baseline to 72 weeks ]

41.  Secondary:   Change in Weight   [ Time Frame: baseline to 72 weeks ]

42.  Secondary:   Change in Body-mass Index   [ Time Frame: baseline to 72 weeks ]

43.  Secondary:   Change in Waist Circumference   [ Time Frame: baseline to 72 weeks ]

44.  Secondary:   Change in Waist-to-hip Ratio   [ Time Frame: baseline to 72 weeks ]

45.  Secondary:   Change in Systolic Blood Pressure   [ Time Frame: baseline to 72 weeks ]

46.  Secondary:   Change in Diastolic Blood Pressure   [ Time Frame: baseline to 72 weeks ]

47.  Secondary:   Change in SF-36 Quality of Life Physical Component Summary   [ Time Frame: baseline to 72 weeks ]

48.  Secondary:   Change in SF-36 Quality of Life Mental Component Summary   [ Time Frame: baseline to 72 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Mark Van Natta
Organization: Johns Hopkins Data Coordinating Centers
phone: 410-614-1362
e-mail: mvannat1@jhu.edu


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01265498     History of Changes
Other Study ID Numbers: NASH-FLINT (IND)
U01DK061730 ( U.S. NIH Grant/Contract )
First Submitted: December 21, 2010
First Posted: December 23, 2010
Results First Submitted: June 26, 2015
Results First Posted: August 21, 2015
Last Update Posted: April 6, 2018