A Study to Assess the Safety, Tolerability, Pharmacokinet... | NCT03421431

Status Module

Name	Class
ICON Clinical Research	INDUSTRY
Triangle Biostatistics, LLC	INDUSTRY

Label	Type	Description	Intervention Names
EDP-305 Dose 1	Experimental	Subjects will take 2 tablets once a day orally for 12 weeks	Drug: EDP-305 Dose 1
EDP-305 Dose 2	Experimental	Subjects will take 2 tablets once a day orally for 12 weeks	Drug: EDP-305 Dose 2
Placebo	Placebo Comparator	Subjects will take 2 tablets once a day orally for 12 weeks	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
EDP-305 Dose 1	Drug	Two tablets daily for 12 weeks	EDP-305 Dose 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Nathalie Adda, MD	Enanta Pharmaceuticals, Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Radiant Research Incorporated		Chandler	Arizona	85224	United States
Central Arizona Medical Associates

PubMed Identifier	Type	Citation	Retractions
34740705	Derived	Ratziu V, Rinella ME, Neuschwander-Tetri BA, Lawitz E, Denham D, Kayali Z, Sheikh A, Kowdley KV, Desta T, Elkhashab M, DeGrauw J, Goodwin B, Ahmad A, Adda N. EDP-305 in patients with NASH: A phase II double-blind placebo-controlled dose-ranging study. J Hepatol. 2022 Mar;76(3):506-517. doi: 10.1016/j.jhep.2021.10.018. Epub 2021 Nov 3.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 21, 2018	Jul 13, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Efficacy Population: included all participants who received at least one dose of the study treatment. Here "Overall Number of Participants Analyzed" = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.

Posted

Mean

Standard Deviation

units per liter (U/L)

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants	OG00020 OG00148 OG00238

Title

Denominators

Categories

Title	Measurements
	OG000-13.85± 18.151 OG001-23.76± 28.135 OG002-26.14± 33.328

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		ANCOVA		0.0495		Least Squares (LS) mean difference	12.460			2-Sided	95	0.029	24.891					Superiority
OG000 OG001		ANCOVA		0.3039

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.

Posted

Mean

Standard Deviation

percentage of fat

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

ratio

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.

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.

Efficacy Population: included all participants who received at least one dose of the study treatment. Here "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.

Posted

Mean

Standard Deviation

millimoles per liter (mmol/L)

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

mmol/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

mmol/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

mmol/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

proteins*10^9/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

proteins*10^9/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

proteins*10^9/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

mmol/L

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

μIU/mL

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg

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.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

percentage of glycated hemoglobin

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here "Overall Number of Participants Analyzed" = participants evaluable for this outcome measure and "Number Analyzed" = participants who were evaluable for specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts

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.

Posted

Median

Full Range

hours (h)

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour*nanogram per milliliter (h*ng/mL)

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Median

Full Range

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Median

Full Range

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Median

Full Range

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Units	Counts
Participants

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)

ID	Title	Description
OG000	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG001	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

kilograms (kg)

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

ratio

Baseline and Week 12

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
OG002	EDP-305 2.5 mg

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.

Posted

Mean

Standard Deviation

nanogram per liter (ng/L)

Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

ng/L

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)

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

ng/mL

Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

ng/mL

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)

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

micromoles per liter (μmol/L)

Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

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.

Posted

Mean

Standard Deviation

μmol/L

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)

ID	Title	Description
OG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
OG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0001 affected24 at risk EG0015 affected55 at risk EG00225 affected53 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected55 at risk EG0024 affected53 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected55 at risk EG0023 affected53 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0001 affected24 at risk EG0013 affected55 at risk EG0022 affected53 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected55 at risk EG0023 affected53 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0002 affected24 at risk EG0011 affected55 at risk EG0021 affected53 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 21.0	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected55 at risk EG0021 affected53 at risk
Headache	Nervous system disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected55 at risk EG0022 affected53 at risk
Dizziness	Nervous system disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0001 affected24 at risk EG0013 affected55 at risk EG0021 affected53 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected55 at risk EG0021 affected53 at risk
Fatigue	General disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected55 at risk EG0022 affected53 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected55 at risk EG0023 affected53 at risk

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Title	Description
BG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.
BG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
BG002	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug.	24	1	24	8	24
EG001	EDP-305 1 mg	EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.	55	1	55	17	55
EG002	EDP-305 2.5 mg	EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks.	53	0	53	32	53

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Cerebrovascular accident	Nervous system disorders	MedDRA Version 21.0	Non-systematic Assessment		EG0001 affected24 at risk EG0010 affected55 at risk EG0020 affected53 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 21.0	Non-systematic Assessment		EG0000 affected24 at risk EG0011 affected55 at risk EG0020 affected53 at risk