A Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis

Non-Alcoholic Steatohepatitis Clinical Trial

Official title:

A Phase 2 Dose Ranging, Randomized, Double Blind, and Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis (NASH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03421431
• Other study ID #: EDP 305-101
• Status: Completed
• Phase: Phase 2
• Start date: April 25, 2018
• Est. completion date: July 10, 2019

Study information

• Verified date: August 2021
• Source: Enanta Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with Non-Alcoholic Steatohepatitis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: July 10, 2019
• Est. primary completion date: June 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• An informed consent document must be signed and dated by the subject

• Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive

• Male or female with presence of NASH by:

• Histologic evidence on a historical liver biopsy within 24 months of Screening consistent with NASH with fibrosis (no cirrhosis), and elevated ALT at Screening AND Screening MRI PDFF with >8 % steatosis OR

• Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or pre-diabetes AND Screening MRI PDFF with >8 % steatosis

• Body mass index (BMI) >25 kg/m2; for Asian-Americans, BMI >23 kg/m2

• Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305.

• Subject must be willing and able to adhere to the assessments, visit schedules, prohibitions and restrictions, as described in this protocol

Exclusion Criteria:

• Laboratory Screening Results:

• Total bilirubin > ULN (normal range 0.2-1.2 mg/dL)

• Total white blood cells (WBC) <3,000 cells/mm3

• Absolute neutrophil count (ANC) <1,500 cells/mm3

• Platelet count <140,000/mm3

• Prothrombin time (international normalized ratio, INR) > 1.2

• Creatine kinase above the upper limit of normal (ULN) except when in relation with intense exercise

• Serum creatinine >2 mg/dL or creatinine clearance <60 ml/min (based on Cockroft Gault method)

• Known history of alpha-1-antitrypsin deficiency

• Use of an experimental treatment for NASH within the past 6 months

• Use of immunosuppressant (eg, corticosteroids) for more than 2 weeks in duration within 1 year prior to Screening and during the course of the study

• Use of experimental or unapproved drugs within a year of Screening

• Any other condition(s) (including cardiovascular diseases) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Principal Investigator (PI)

• Pregnant or nursing females

• Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by a Model for End-Stage Liver Disease (MELD) Score = 15

• Clinical suspicion of advanced liver disease or cirrhosis

• Coexisting liver or biliary diseases, such as primary sclerosing cholangitis (PSC), choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis

• Suspicion of cancer (eg, liver cancer) with the exception of basal cell carcinoma that has been resected

• Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2xULN

• Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 µmol/L)

• Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)

• Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to Screening)

• Subject has received an investigational agent or vaccine within 30 days, or a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to the planned intake of study drug. NOTE: Flu vaccine will be allowed upon Medical Monitor's approval

• Use of a new statin regimen from Screening and throughout study duration. NOTE:

Subjects on a stable dose of statins for at least three months prior to Screening are allowed. No dose modification during the study will be allowed.

• Current use of fibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate

• Clinically significant history of drug sensitivity or allergy, as determined by the PI

• Uncontrolled diabetes mellitus (ie, HbA1c =9% or higher) 60 days prior to Day 1

• Subjects with contraindications to MRI imaging, or not being able to have the MRI performed

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-Alcoholic Steatohepatitis

Intervention

Drug:
• EDP-305 Dose 1
Two tablets daily for 12 weeks
• EDP-305 Dose 2
Two tablets daily for 12 weeks
• Placebo
Two tablets daily for 12 weeks

Locations

Country	Name	City	State
Canada	Aggarwal and Associates Limited	Brampton	Ontario
Canada	Chronic Viral Illness Service McGill University Health Center/Royal Victoria	Montreal	Quebec
Canada	Clinique de recherche Medpharmgene	Montreal	Quebec
Canada	Toronto Liver Centre	Toronto	Ontario
France	Hopital Pitie Salpetriere	Paris
France	CHU de Bordeaux - GH Sud - Hoital Haut Leveque	Pessac
France	CHU de Strasbourg - Nouvel Hôspital Civil	Strasbourg
New Zealand	Auckland Clinical Studies Limited	Auckland
Puerto Rico	Latin Clinical Trial Center	San Juan
United Kingdom	Addenbrookes Hospital (AH)-Cambridge University Hospitals NHS Foundation Trust	Cambridge	Cambridgeshire
United Kingdom	King's College Hospital NHS Foundation	London	Greater London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	Nottinghamshire
United States	Anaheim Clinical Trials	Anaheim	California
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Texas Diabetes & Endocrinology	Austin	Texas
United States	Mercy Medical Center	Baltimore	Maryland
United States	Digestive Disease Associates, PA	Catonsville	Maryland
United States	Radiant Research Incorporated	Chandler	Arizona
United States	Carolinas Medical Center Transplant Center/Center for Liver Disease	Charlotte	North Carolina
United States	Feinberg School of Medicine Northwestern University	Chicago	Illinois
United States	estudy site - Chula Vista	Chula Vista	California
United States	Sterling Research Group, Ltd.	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Clinical Research Advantage, Inc. / Colorado Springs Family Practice	Colorado Springs	Colorado
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	Southern California Research Center	Coronado	California
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	AGA Clinical Research Associates, LLC	Egg Harbor Township	New Jersey
United States	South Denver Gastroenterology,P.C.	Englewood	Colorado
United States	Fleming Island Center for Clinical Research	Fleming Island	Florida
United States	Fresno Clinical Research Center (FCRC)	Fresno	California
United States	Gastroenterology Associates, PC	Gainesville	Virginia
United States	DHAT Research Institute	Garland	Texas
United States	Baylor College of Medicine - Advanced Liver Therapies	Houston	Texas
United States	Carolinas Center for Liver Disease / Carolinas Health Care System	Huntersville	North Carolina
United States	Midwest Institute For Clinical Research	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Jacksonville Center for Endoscopy - Southside ; Borland Groover Clinic	Jacksonville	Florida
United States	Westside Center for Clinical Research	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Mayo Clinic Health System - Franciscan Healthcare	La Crosse	Wisconsin
United States	UCSD Altman Clinical and Translational Research Institute	La Jolla	California
United States	Precision Clinical Research, LLC.	Lauderdale Lakes	Florida
United States	Wasatch Peak Family Practice/Radiant Research, Inc	Layton	Utah
United States	Clinical Trials Research	Lincoln	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	National Research Institute	Los Angeles	California
United States	Northwell Health Inc.	Manhasset	New York
United States	Gastrointestinal Specialists Of Georgia	Marietta	Georgia
United States	University Of Tennessee Health Science Center	Memphis	Tennessee
United States	Central Arizona Medical Associates	Mesa	Arizona
United States	Florida Advanced Medical Research, Inc.	Miami	Florida
United States	Homestead Medical Research	Miami	Florida
United States	Research Associates of South Florida, LLC	Miami	Florida
United States	Ocean Blue Medical Research Center, Inc	Miami Springs	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Radiant Research, Inc.	Murray	Utah
United States	Quality Medical Research, PLLC	Nashville	Tennessee
United States	Oshsner Clinic Foundation	New Orleans	Louisiana
United States	NYU Langone Medical Center - The Center for Musculoskeletal Care (CMC)	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Bon Secours St. Mary's Hospital of Richmond, Inc	Newport News	Virginia
United States	Clinical Neuroscience Solutions Inc.	Orlando	Florida
United States	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida
United States	Mayo Clinic Specialty Building	Phoenix	Arizona
United States	University of Pittsburgh Medical Center - Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	The Gastroenterology Group, PC	Reston	Virginia
United States	Inland Empire Liver Foundation	Rialto	California
United States	Saint Louis University	Saint Louis	Missouri
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Radiant Research, Inc.	San Antonio	Texas
United States	Texas Liver Institute	San Antonio	Texas
United States	Southern California Transplantation Institute Research Foundation	San Clemente	California
United States	Precision Research Institute	San Diego	California
United States	Swedish Medical Center-Swedish Organ Transplant and Liver Center	Seattle	Washington
United States	University of Washington / Harborview Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	WestGlen Gastrointestinal Consultants, PA	Shawnee Mission	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Enanta Pharmaceuticals	ICON Clinical Research, Triangle Biostatistics

Countries where clinical trial is conducted

United States,  Canada,  France,  New Zealand,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ALT level. Baseline refers to the average of the screening and the Day 1 values; if either the screening or Day 1 values were missing, the non-missing value was used. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12	The liver fat percentage was assessed by MRI-PDFF, which is an established method that enables the quantification of fat content in the liver; the value of liver fat is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the aspartate aminotransferase (AST) level and platelet count. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. The APRI score (AST to platelet ratio index) is an index comprised of biochemical values and is used to determine the degree of hepatic fibrosis. APRI is calculated from the level of AST measured in a blood test (international units per liter [IU/L]) and platelet count (10^9/L) according to the following formula: APRI = ([AST value in IU/L / upper limit of the normal range of AST] / [platelet count in 10^9/L]) × 100.; In general, APRI scores range from 0 to >2.0, where scores <0.5 indicate no significant fibrosis, scores >1.5 indicate significant fibrosis, and scores >2.0 have been shown to be best correlated with the presence of cirrhosis. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Triglycerides (TG) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the TG level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Total Cholesterol at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the total cholesterol level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the LDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Adiponectin at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the adiponectin level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoA-1 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoB level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoC3 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Fasting Blood Glucose at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting glucose level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Fasting Insulin at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting insulin (in micro International units per milliliter [µIU/mL]). Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were not considered as having type 2 diabetes mellitus (T2DM) were identified as nondiabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were considered as having T2DM were identified as diabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12	Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HbA1c. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the Pharmacokinetic (PK) Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12	The Tmax was measured for EDP-305 on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Cmax of EP-022571 on Day 1 and at Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Tmax of EP-022571 on Day 1 and at Week 12	The Tmax was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	AUC(Last) of EP-022571 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Cmax of EP-022572 on Day 1 and at Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Tmax of EP-022572 on Day 1 and at Week 12	The Tmax was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	AUC(Last) of EP-022572 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Cmax of EP-022679 on Day 1 and at Week 12	The Cmax is the maximum observed plasma concentration, which was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Tmax of EP-022679 on Day 1 and at Week 12	The Tmax was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	AUC(Last) of EP-022679 on Day 1 and at Week 12	AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.	Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Secondary	Mean Change From Baseline in Body Weight at Week 12	Body weight was measured at specific timepoints for the participants. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12	The WTH ratio is calculated as the ratio of waist to hip circumference, which was measured at specific timepoints. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Baseline and Week 12
Secondary	Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12	Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Secondary	Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12	Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Secondary	Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12	Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Secondary	Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12	Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Secondary	Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12	Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Secondary	Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12	Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.	Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)