Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    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)

    Summary
    EudraCT number
    		 2017-004365-27
    Trial protocol
    		 FR   GB  
    Global end of trial date
    10 Jul 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Jun 2021
    First version publication date
    10 Jun 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EDP-305-101
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03421431
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Enanta Pharmaceuticals, Inc.
    Sponsor organisation address
    500 Arsenal St., Watertown, United States, MA 02472
    Public contact
    Maria Gawryl, Enanta Pharmaceuticals, Inc., mgawryl@enanta.com
    Scientific contact
    Maria Gawryl, Enanta Pharmaceuticals, Inc., mgawryl@enanta.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Jul 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Jul 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Jul 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the study were to: - Evaluate change in alanine aminotransferase (ALT) levels - Evaluate the safety and tolerability of EDP-305 The secondary objectives of the study were to: - Evaluate the effect of EDP-305 on liver fat - Evaluate the effect of EDP-305 on fibrosis (liver stiffness) - Evaluate the effect of EDP-305 on noninvasive liver fibrosis markers - Evaluate the effects of EDP-305 on lipids - Evaluate the effects of EDP-305 on glucose metabolism - Evaluate the effects of EDP-305 on inflammatory markers - Evaluate the PK of EDP-305 and its metabolites in plasma - Evaluate the effect of EDP-305 on body weight - Evaluate the effect of EDP-305 on waist-to-hip (WTH) ratio - Evaluate the Pharmacodynamic (PD) of EDP-305
    Protection of trial subjects
    This study was conducted in accordance with current applicable regulations, international council on Harmonisation (ICH) guidelines and local legal requirements. It complies with the ethical principles described in the 18th World Medical Assembly (Helsinki 1964) and amendments of the 29th (Tokyo 1975), 35th (Venice 1983), the 41st (Hong Kong 1989) and the 48th (South Africa 1996) World Medical Assemblies, Declaration of Helsinki. From a safety perspective, appropriate study restrictions based on the mechanism of action of EDP-305 (i.e., farnesoid X receptor agonistic effect) were implemented including screening procedures and exclusion criteria to mitigate and minimise the risks and to ensure the safety of subjects. Each subject signed an informed consent form (ICF) containing appropriate study and study drug information and was provided a copy of the ICF.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Jan 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    New Zealand: 1
    Country: Number of subjects enrolled
    United States: 120
    Worldwide total number of subjects
    134
    EEA total number of subjects
    4
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    122
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Out of 134 randomised subjects, 2 subjects (1 subject each in the EDP-305 2.5 mg and placebo groups) were randomised but not dosed because the subjects withdrew and were not included in the Safety and Efficacy Populations.

    Pre-assignment period milestones
    Number of subjects started
    		 134
    Intermediate milestone: Number of subjects
    Number of subjects randomised: 134
    Number of subjects completed
    		 132

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Randomised but not dosed: 2
    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 A total of 24 subjects received at least one dose of placebo out of 25 randomised subjects, 1 subject withdrew the consent before dosing on Day 1 and was not dosed in the study followed by excluded from the Safety and Efficacy Populations.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    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.

    Arm title
    		 EDP-305 1 mg
    Arm description
    		 All the 55 randomised subjects received at least one dose of EDP-305 1 mg and were included in the Safety and Efficacy Populations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    EDP-305 1 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    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.

    Arm title
    		 EDP-305 2.5 mg
    Arm description
    		 A total of 53 subjects received at least one dose of EDP-305 2.5 mg out of 54 randomised subjects, 1 subject withdrew the consent before dosing on Day 1 and was not dosed in the study followed by excluded from the Safety and Efficacy Populations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    EDP-305 2.5 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    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.

    Number of subjects in period 1 [1]
    		Placebo EDP-305 1 mg EDP-305 2.5 mg
    Started
    24
    55
    53
    Completed
    18
    49
    39
    Not completed
    6
    6
    14
         Stopping rules
    -
    1
    -
         Consent withdrawn by subject
    3
    2
    1
         Adverse event, non-fatal
    2
    1
    12
         Lost to follow-up
    1
    1
    1
         Protocol deviation
    -
    1
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Number of subjects included all the randomised subjects who received at least one dose of the study treatment (n = 132 [same for both Safety and Efficacy Populations]). Out of 134 randomised subjects, 2 subjects (1 subject each in the EDP-305 2.5 mg and placebo groups) discontinued the study due to withdrawal of consent before dosing (on Day 1) and were excluded from the Safety and Efficacy Populations.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 A total of 24 subjects received at least one dose of placebo out of 25 randomised subjects, 1 subject withdrew the consent before dosing on Day 1 and was not dosed in the study followed by excluded from the Safety and Efficacy Populations.

    Reporting group title
    EDP-305 1 mg
    Reporting group description
    		 All the 55 randomised subjects received at least one dose of EDP-305 1 mg and were included in the Safety and Efficacy Populations.

    Reporting group title
    EDP-305 2.5 mg
    Reporting group description
    		 A total of 53 subjects received at least one dose of EDP-305 2.5 mg out of 54 randomised subjects, 1 subject withdrew the consent before dosing on Day 1 and was not dosed in the study followed by excluded from the Safety and Efficacy Populations.

    Reporting group values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg Total
    Number of subjects
    		 24 55 53 132
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 22 52 46 120
        From 65-84 years
    		 2 3 7 12
        85 years and over
    		 0 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 11 29 29 69
        Male
    		 13 26 24 63
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 0 1
        Asian
    		 1 7 3 11
        Black or African American
    		 2 1 0 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        White
    		 17 42 47 106
        Not reported
    		 2 2 1 5
        Other
    		 0 0 1 1
        Mexican
    		 1 1 1 3
        Not specified
    		 0 2 0 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 A total of 24 subjects received at least one dose of placebo out of 25 randomised subjects, 1 subject withdrew the consent before dosing on Day 1 and was not dosed in the study followed by excluded from the Safety and Efficacy Populations.

    Reporting group title
    EDP-305 1 mg
    Reporting group description
    		 All the 55 randomised subjects received at least one dose of EDP-305 1 mg and were included in the Safety and Efficacy Populations.

    Reporting group title
    EDP-305 2.5 mg
    Reporting group description
    		 A total of 53 subjects received at least one dose of EDP-305 2.5 mg out of 54 randomised subjects, 1 subject withdrew the consent before dosing on Day 1 and was not dosed in the study followed by excluded from the Safety and Efficacy Populations.

    Subject analysis set title
    EDP-305 1 mg (PK Population)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic (PK) Population included all subjects who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint.

    Subject analysis set title
    EDP-305 2.5 mg (PK Population)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The PK Population included all subjects who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint.

    Primary: Mean Change From Baseline (Average) in ALT at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline (Average) in ALT at Week 12
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    48
    38
    Units: unit(s)/litre
        arithmetic mean (standard deviation)
    -13.85 ± 18.151
    -23.76 ± 28.135
    -26.14 ± 33.328
    Statistical analysis title
    		 Placebo versus (v) EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0495
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares (LS) mean difference
    Point estimate
    12.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.029
         upper limit
    		 24.891
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3039
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    6.257
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.754
         upper limit
    		 18.268
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.213
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    6.203
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.615
         upper limit
    		 16.021

    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

    		 Close Top of page
    End point title
    		 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
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    51
    49
    Units: percentage of fat
        arithmetic mean (standard deviation)
    -2.842 ± 4.4687
    -3.759 ± 5.1600
    -6.428 ± 7.2586
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0009
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    4.717
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.98
         upper limit
    		 7.455
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4946
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.934
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.766
         upper limit
    		 3.635
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0005
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    3.783
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.708
         upper limit
    		 5.858

    Secondary: Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12
    End point description
    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 litre [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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    17
    44
    35
    Units: ratio
        arithmetic mean (standard deviation)
    -0.180 ± 0.3462
    -0.107 ± 0.3396
    -0.194 ± 0.3533
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2756
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.076
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.062
         upper limit
    		 0.214
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9686
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.003
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.136
         upper limit
    		 0.131
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1406
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.079
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.026
         upper limit
    		 0.184

    Secondary: Mean Change From Baseline in Triglycerides (TG) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Triglycerides (TG) at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    48
    38
    Units: millimole(s)/litre
        arithmetic mean (standard deviation)
    -0.151 ± 0.8529
    -0.366 ± 1.5858
    0.129 ± 1.1088
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.613
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.125
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.613
         upper limit
    		 0.363
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8366
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.049
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.521
         upper limit
    		 0.423
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7015
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.076
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.466
         upper limit
    		 0.315

    Secondary: Mean Change From Baseline in Total Cholesterol at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Total Cholesterol at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    49
    38
    Units: millimole(s)/litre
        arithmetic mean (standard deviation)
    -0.175 ± 0.6879
    0.046 ± 0.6697
    -0.003 ± 1.0046
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3875
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.186
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.613
         upper limit
    		 0.24
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2331
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.248
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.657
         upper limit
    		 0.162
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7164
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.061
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.272
         upper limit
    		 0.395

    Secondary: Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    49
    38
    Units: millimole(s)/litre
        arithmetic mean (standard deviation)
    0.008 ± 0.1279
    -0.058 ± 0.1670
    -0.210 ± 0.2708
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.11
         upper limit
    		 0.311
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.348
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.046
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.051
         upper limit
    		 0.143
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.164
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.085
         upper limit
    		 0.243

    Secondary: Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    44
    37
    Units: millimole(s)/litre
        arithmetic mean (standard deviation)
    -0.112 ± 0.6431
    0.129 ± 0.5099
    0.151 ± 0.8157
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0897
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.299
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.645
         upper limit
    		 0.047
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1411
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.251
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.586
         upper limit
    		 0.085
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.733
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.048
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.326
         upper limit
    		 0.23

    Secondary: Mean Change From Baseline in Adiponectin at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Adiponectin at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    48
    38
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    319.16 ± 689.387
    17.94 ± 828.494
    522.00 ± 2649.701
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9143
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    51.873
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -901.574
         upper limit
    		 1005.32
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3718
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    404.168
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -489.519
         upper limit
    		 1297.854
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3466
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -352.295
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1091.308
         upper limit
    		 386.719

    Secondary: Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    49
    38
    Units: x 10^9/litre
        arithmetic mean (standard deviation)
    -0.074 ± 0.1514
    -0.107 ± 0.1671
    -0.226 ± 0.2197
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0003
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.081
         upper limit
    		 0.264
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5685
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.025
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.062
         upper limit
    		 0.113
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.147
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.075
         upper limit
    		 0.219

    Secondary: Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    49
    38
    Units: x 10^9/litre
        arithmetic mean (standard deviation)
    -0.028 ± 0.1687
    0.040 ± 0.1781
    0.099 ± 0.2898
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0282
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.133
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.252
         upper limit
    		 -0.015
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2412
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.068
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.182
         upper limit
    		 0.046
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1649
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.066
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.158
         upper limit
    		 0.027

    Secondary: Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    49
    38
    Units: x 10^9/litre
        arithmetic mean (standard deviation)
    -0.0094 ± 0.04388
    -0.0167 ± 0.03918
    -0.0122 ± 0.05721
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4357
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.009
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.014
         upper limit
    		 0.032
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8989
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.021
         upper limit
    		 0.023
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.412
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.008
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.011
         upper limit
    		 0.026

    Secondary: Mean Change From Baseline in Fasting Blood Glucose at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Fasting Blood Glucose at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    48
    38
    Units: millimole(s)/litre
        arithmetic mean (standard deviation)
    -0.11 ± 2.130
    0.48 ± 1.847
    1.68 ± 3.396
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0134
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -1.731
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.095
         upper limit
    		 -0.368
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6263
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.327
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.656
         upper limit
    		 1.001
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0115
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -1.404
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.487
         upper limit
    		 -0.322

    Secondary: Mean Change From Baseline in Fasting Insulin at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Fasting Insulin at Week 12
    End point description
    Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting insulin. 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    47
    38
    Units: micro international unit(s)/millilitre
        arithmetic mean (standard deviation)
    -0.688 ± 9.2808
    2.528 ± 14.6947
    -5.635 ± 52.7637
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4608
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -3.723
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.7
         upper limit
    		 6.253
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6238
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -2.377
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.962
         upper limit
    		 7.207
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7367
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -1.346
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.268
         upper limit
    		 6.576

    Secondary: Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Subjects at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Subjects at Week 12
    End point description
    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 subjects using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Subjects 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    3
    11
    13
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.587 ± 2.0088
    0.192 ± 2.7180
    -6.474 ± 24.9369
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8302
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.407
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.287
         upper limit
    		 3.474
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5053
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -1.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.192
         upper limit
    		 2.632
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.476
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.873
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.62
         upper limit
    		 3.366

    Secondary: Mean Change From Baseline in HOMA Index for Diabetic Subjects at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in HOMA Index for Diabetic Subjects at Week 12
    End point description
    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 subjects using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Subjects 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    17
    35
    25
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.493 ± 6.2624
    2.088 ± 6.6114
    5.059 ± 15.0113
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0639
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -5.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.171
         upper limit
    		 0.351
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4884
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -2.064
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.971
         upper limit
    		 3.843
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1532
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -3.846
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.156
         upper limit
    		 1.464

    Secondary: Mean Change From Baseline in Glycated Haemoglobin (HbA1c) in Subjects With T2DM at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Glycated Haemoglobin (HbA1c) in Subjects With T2DM at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    17
    38
    25
    Units: percent
        arithmetic mean (standard deviation)
    0.31 ± 0.685
    0.21 ± 0.776
    0.76 ± 0.963
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0811
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.978
         upper limit
    		 0.058
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6312
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.117
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.367
         upper limit
    		 0.601
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0099
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.577
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.011
         upper limit
    		 -0.143

    Secondary: Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12

    		 Close Top of page
    End point title
    		 Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [1]
    52 [2]
    Units: nanogram(s)/millilitre
    geometric mean (geometric coefficient of variation)
        Day 1
    11.1 ± 105
    25.1 ± 101
        Week 12
    15.9 ± 105
    41.1 ± 101
    Notes
    [1] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [2] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [3]
    52 [4]
    Units: hour
    median (full range (min-max))
        Day 1
    6.00 (2.00 to 8.07)
    6.00 (2.00 to 8.25)
        Week 12
    6.00 (0.00 to 8.02)
    6.00 (0.00 to 8.18)
    Notes
    [3] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [4] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    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

    		 Close Top of page
    End point title
    		 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
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and at Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [5]
    52 [6]
    Units: hour*nanogram/millilitre (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        Day 1
    53.6 ± 101
    129 ± 100
        Week 12
    87.2 ± 101
    264 ± 100
    Notes
    [5] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [6] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 12
    No statistical analyses for this end point

    Secondary: Cmax of EP-022571 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Cmax of EP-022571 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [7]
    52 [8]
    Units: nanogram(s)/millilitre
    geometric mean (geometric coefficient of variation)
        Day 1
    0.324 ± 983
    0.833 ± 177
        Week 12
    0.296 ± 1549
    0.787 ± 233
    Notes
    [7] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [8] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: Tmax of EP-022571 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Tmax of EP-022571 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [9]
    52 [10]
    Units: hour
    median (full range (min-max))
        Day 1
    6.00 (2.00 to 8.00)
    6.00 (1.93 to 8.25)
        Week 12
    6.00 (0.00 to 8.00)
    6.00 (0.00 to 6.15)
    Notes
    [9] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [10] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: AUC(Last) of EP-022571 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 AUC(Last) of EP-022571 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and at Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [11]
    52 [12]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    1.48 ± 174
    3.77 ± 112
        Week 12
    1.41 ± 187.01
    3.81 ± 121.18
    Notes
    [11] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [12] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 12
    No statistical analyses for this end point

    Secondary: Cmax of EP-022572 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Cmax of EP-022572 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [13]
    52 [14]
    Units: nanogram(s)/millilitre
    geometric mean (geometric coefficient of variation)
        Day 1
    0.234 ± 1942
    0.571 ± 212
        Week 12
    0.214 ± 2863
    0.556 ± 212
    Notes
    [13] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [14] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: Tmax of EP-022572 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Tmax of EP-022572 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [15]
    52 [16]
    Units: hour
    median (full range (min-max))
        Day 1
    6.00 (2.00 to 8.07)
    6.00 (2.00 to 8.00)
        Week 12
    6.00 (0.00 to 8.00)
    2.05 (0.00 to 8.18)
    Notes
    [15] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [16] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: AUC(Last) of EP-022572 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 AUC(Last) of EP-022572 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [17]
    52 [18]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    1.06 ± 220
    2.92 ± 114
        Week 12
    1.13 ± 212
    3.19 ± 116
    Notes
    [17] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [18] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 12
    No statistical analyses for this end point

    Secondary: Cmax of EP-022679 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Cmax of EP-022679 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [19]
    52 [20]
    Units: nanogram(s)/millilitre
    geometric mean (geometric coefficient of variation)
        Day 1
    0.574 ± 321
    1.28 ± 167
        Week 12
    1.41 ± 117
    3.85 ± 122
    Notes
    [19] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [20] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: Tmax of EP-022679 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 Tmax of EP-022679 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [21]
    52 [22]
    Units: hour
    median (full range (min-max))
        Day 1
    8.00 (5.88 to 8.00)
    8.00 (6.00 to 8.25)
        Week 12
    6.03 (0.00 to 8.00)
    6.00 (0.00 to 8.18)
    Notes
    [21] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [22] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 13
    No statistical analyses for this end point

    Secondary: AUC(Last) of EP-022679 on Day 1 and at Week 12

    		 Close Top of page
    End point title
    		 AUC(Last) of EP-022679 on Day 1 and at Week 12
    End point description
    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 subjects in the PK Population.
    End point type
    Secondary
    End point timeframe
    Day 1 and Week 12
    End point values
    		 EDP-305 1 mg (PK Population) EDP-305 2.5 mg (PK Population)
    Number of subjects analysed
    54 [23]
    52 [24]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1
    2.32 ± 137.54
    5.09 ± 117
        Week 12
    7.14 ± 113
    22.5 ± 104
    Notes
    [23] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 17
    [24] - Number of subjects analysed for Day 1 = 19 Number of subjects analysed for Week 12 = 12
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Body Weight at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Body Weight at Week 12
    End point description
    Body weight was measured at specific timepoints for the subjects. 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    20
    49
    38
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    -0.877 ± 2.8100
    -1.440 ± 2.7984
    -2.114 ± 3.2829
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.112
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    1.356
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.322
         upper limit
    		 3.034
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4229
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.647
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.947
         upper limit
    		 2.24
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2764
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.577
         upper limit
    		 1.996

    Secondary: Mean Change From Baseline in WTH Ratio at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in WTH Ratio at Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    19
    49
    38
    Units: ratio
        arithmetic mean (standard deviation)
    0.013 ± 0.0729
    -0.007 ± 0.0477
    0.014 ± 0.0509
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    EDP-305 2.5 mg v Placebo
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5606
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.008
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.037
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1002
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.004
         upper limit
    		 0.05
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2002
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.014
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.036
         upper limit
    		 0.008

    Secondary: Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive PD Samples) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive PD Samples) at Week 12
    End point description
    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 pre-dose 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 (8 hours post-dose)
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    8
    18
    14
    Units: nanogram(s)/litre
        arithmetic mean (standard deviation)
    159.98 ± 165.245
    410.00 ± 260.223
    607.12 ± 891.553
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7014
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -178.787
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1098.454
         upper limit
    		 740.88
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    26
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.907
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    52.307
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -830.934
         upper limit
    		 935.547
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.536
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -231.094
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -967.273
         upper limit
    		 505.086

    Secondary: Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12
    End point description
    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 pre-dose 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 (pre-dose)
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    9
    23
    17
    Units: nanogram(s)/litre
        arithmetic mean (standard deviation)
    33.51 ± 155.744
    46.04 ± 88.662
    813.29 ± 3200.567
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    26
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2985
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -753.153
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2183.92
         upper limit
    		 677.614
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8413
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    139.107
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1236.689
         upper limit
    		 1514.902
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1168
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -892.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2011.705
         upper limit
    		 227.186

    Secondary: Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12
    End point description
    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 pre-dose 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 (8 hours post-dose)
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    8
    17
    14
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    -9.484 ± 20.6295
    -36.783 ± 24.6560
    -40.567 ± 20.9260
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    33.491
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.984
         upper limit
    		 48.998
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    30.814
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.802
         upper limit
    		 45.825
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6757
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    2.677
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.946
         upper limit
    		 15.3

    Secondary: Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12
    End point description
    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 pre-dose 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 (pre-dose)
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    9
    25
    18
    Units: nanogram(s)/millilitre
        arithmetic mean (standard deviation)
    -5.242 ± 30.5321
    -13.500 ± 26.2458
    -23.773 ± 20.7045
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0134
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    21.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.533
         upper limit
    		 38.067
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4686
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    5.847
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.116
         upper limit
    		 21.811
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0181
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    15.453
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.699
         upper limit
    		 28.206

    Secondary: Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12
    End point description
    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 pre-dose 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 (8 hours post-dose)
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    7
    18
    14
    Units: micromole(s)/litre
        arithmetic mean (standard deviation)
    4.47 ± 3.668
    2.16 ± 5.507
    0.14 ± 3.125
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    Placebo v EDP-305 2.5 mg
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0557
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    4.324
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.108
         upper limit
    		 8.756
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2867
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    2.305
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.955
         upper limit
    		 6.566
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2437
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.2437
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.39
         upper limit
    		 5.429

    Secondary: Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12
    End point description
    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 pre-dose 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12 (pre-dose)
    End point values
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Number of subjects analysed
    9
    25
    17
    Units: micromole(s)/litre
        arithmetic mean (standard deviation)
    0.77 ± 5.789
    -0.11 ± 2.783
    0.74 ± 4.091
    Statistical analysis title
    		 Placebo v EDP-305 2.5 mg
    Comparison groups
    EDP-305 2.5 mg v Placebo
    Number of subjects included in analysis
    26
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9913
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.019
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.491
         upper limit
    		 3.53
    Statistical analysis title
    		 Placebo v EDP-305 1 mg
    Comparison groups
    Placebo v EDP-305 1 mg
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.553
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.995
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.323
         upper limit
    		 4.314
    Statistical analysis title
    		 EDP-305 1 mg v EDP-305 2.5 mg
    Comparison groups
    EDP-305 1 mg v EDP-305 2.5 mg
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4729
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.976
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.665
         upper limit
    		 1.713

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were reported from the date of signing the consent form to the date of completion of the subject's end of the study visit (Week 16). Ongoing AEs were followed beyond the end of the study visit at the discretion of the investigator.
    Adverse event reporting additional description
    Treatment-emergent adverse events were summarised for the Safety Population, which included all the randomised subjects who received at least one dose of the study treatment.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Out of 25 randomised subjects, 1 subject in the placebo group was not dosed due to consent withdrawal by the subject and was not included in Safety Population. Hence, AE details are presented for 24 subjects (Safety Population).

    Reporting group title
    EDP-305 1 mg
    Reporting group description
    		 All the 55 randomised subjects in the EDP-305 1 mg were dosed and were included in the Safety Population.

    Reporting group title
    EDP-305 2.5 mg
    Reporting group description
    		 Out of 54 randomised subjects, 1 subject in the EDP-305 2.5 mg group was not dosed due to consent withdrawal by the subject and was not included in Safety Population. Hence, AE details are presented for 53 subjects (Safety Population).

    Serious adverse events
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 55 (1.82%)
    0 / 53 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 55 (1.82%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo EDP-305 1 mg EDP-305 2.5 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 24 (33.33%)
    17 / 55 (30.91%)
    32 / 53 (60.38%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 55 (3.64%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    2
    Dizziness
         subjects affected / exposed
    1 / 24 (4.17%)
    3 / 55 (5.45%)
    1 / 53 (1.89%)
         occurrences all number
    1
    3
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 55 (3.64%)
    2 / 53 (3.77%)
         occurrences all number
    2
    2
    2
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 24 (4.17%)
    3 / 55 (5.45%)
    2 / 53 (3.77%)
         occurrences all number
    1
    3
    2
    Diarrhoea
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 55 (3.64%)
    3 / 53 (5.66%)
         occurrences all number
    0
    2
    3
    Vomiting
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 55 (1.82%)
    1 / 53 (1.89%)
         occurrences all number
    2
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 55 (1.82%)
    3 / 53 (5.66%)
         occurrences all number
    0
    1
    3
    Skin and subcutaneous tissue disorders
    Pruritus generalised
         subjects affected / exposed
    1 / 24 (4.17%)
    5 / 55 (9.09%)
    25 / 53 (47.17%)
         occurrences all number
    1
    6
    32
    Rash
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 55 (1.82%)
    4 / 53 (7.55%)
         occurrences all number
    0
    1
    7
    Pruritus
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 55 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    1
    0
    3
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 24 (0.00%)
    3 / 55 (5.45%)
    1 / 53 (1.89%)
         occurrences all number
    0
    3
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 24 (0.00%)
    3 / 55 (5.45%)
    1 / 53 (1.89%)
         occurrences all number
    0
    3
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 00:03:45 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA