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    Clinical Trial Results:
    Lean Efficacy Phase IIa Proof of concept trial (LEAAP). A multi-centre, double-blind, placebo controlled, randomised study in overweight and obese patients during twenty-six weeks, investigating the effect of EMP16-02 on body weight, safety and clinical biomarkers

    Summary
    EudraCT number
    		 2019-004545-32
    Trial protocol
    		 SE  
    Global end of trial date
    30 Aug 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Sep 2022
    First version publication date
    08 Sep 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    EP-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Empros Pharma AB
    Sponsor organisation address
    Nanna Svartz väg 4, Solna, Sweden, SE-171 65
    Public contact
    Arvid Söderhäll, Empros Pharma AB, +46 707233363, arvid.soderhall@emprospharma.com
    Scientific contact
    Arvid Söderhäll, Empros Pharma AB, +46 707233363, arvid.soderhall@emprospharma.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 Aug 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Aug 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Aug 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of the study drug EMP16-02 (120 mg orlistat [O]/40 mg acarbose [A]) on relative body weight loss after a 26-week period of oral treatment as compared to placebo.
    Protection of trial subjects
    The ICFs included information that the data that were recorded, collected and processed could be transferred to the European Economic Area (EEA) or non-EEA countries. In accordance with the General Data protection Regulation (GDPR) (EU) 2016/679, the data did not allow for identification of any persons taking part in the study. The potential study patient was informed that by signing the ICF he/she approved that authorized representatives from the Sponsor and CTC, the concerned Ethical Committee (EC) and CA had direct access to his/her medical records for verification of clinical study procedures. This agreement was substantiated in a separate document, according to local requirements. The patient had the right to request access to his/her personal data and the right to request rectification of any data that were not correct and/or complete. The Investigator had to file a Patient Identification List which included sufficient information to link records, i.e. the eCRF and clinical records. This list will be preserved for possible future inspections/audits but will not be made available to the Sponsor except for monitoring or auditing purposes.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 May 2020
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Scientific research
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Sweden: 156
    Worldwide total number of subjects
    156
    EEA total number of subjects
    156
    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)
    135
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The subjects were recruited from CTC’s database of healthy volunteers and patients, and from advertising in media (including social media).

    Pre-assignment
    Screening details
    		 A total of 209 patients were screened and 156 were randomized (52 patients per treatment group). Thirty-seven patients were screening failures, 6 withdrew consent prior to randomization and 10 were not randomized due to other reasons (fulfilled eligibility criteria but were not needed in the study).

    Period 1
    Period 1 title
    Main study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    This was a double-blind study, and the allocation of treatments was not disclosed until clean file had been declared and the database had been locked. Active treatment and placebo capsules were identical in appearance.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 EMP16-02 - 120/40
    Arm description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02 -120/40 (120 mg orlistat/40 mg acarbose).
    Arm type
    		 Experimental

    Investigational medicinal product name
    EMP16-02
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The drug product, EMP16-02, is a fixed dose combination (FDC) that contains 2 active pharmaceutical ingredients (APIs), namely orlistat (O) and acarbose (A). The IMP was supplied as oral modified release (MR) capsules in 2 different strengths: 60 mg O/20 mg A and 90 mg O/30 mg A. The dose used in this treatment arm was 120 mg O/40 mg A (2 capsules EMP16-02-60/20). The IMP was to be taken halfway into a meal 3 times daily (TID) with approximately 100-200 mL water or other drink. The IMP was not to be taken on an empty stomach. The patients were recommended to leave 3-4 h between each meal/IMP dose. The patients started with a titration period of 6 weeks during which the dose was sequentially increased in order to let patients gradually adapt to the acarbose dose. The IMP was administered TID also during the titration period. At week 7, all patients had reached their final intended dose and a 20-week treatment and observation period started.

    Arm title
    		 EMP16-02 - 150/50
    Arm description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02-150/50 (150 mg orlistat/50 mg acarbose).
    Arm type
    		 Experimental

    Investigational medicinal product name
    EMP16-02
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The drug product, EMP16-02, is a fixed dose combination (FDC) that contains 2 active pharmaceutical ingredients (APIs), namely orlistat (O) and acarbose (A). The IMP was supplied as oral modified release (MR) capsules in 2 different strengths: 60 mg O/20 mg A and 90 mg O/30 mg A. The dose used in this treatment arm was 150 mg O/50 mg A (1 capsule EMP16-02-90/30 and 1 capsule EMP16-02-60/20). The IMP was to be taken halfway into a meal 3 times daily (TID) with approximately 100-200 mL water or other drink. The IMP was not to be taken on an empty stomach. The patients were recommended to leave 3-4 h between each meal/IMP dose. The patients started with a titration period of 6 weeks during which the dose was sequentially increased in order to let patients gradually adapt to the acarbose dose. The IMP was administered TID also during the titration period. At week 7, all patients had reached their final intended dose and a 20-week treatment and observation period started.

    Arm title
    		 Placebo
    Arm description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was a matching, oral capsule containing only cellulose. The IMP was to be taken halfway into a meal 3 times daily (TID) for 26 weeks, together with approximately 100-200 mL water or other drink. The IMP was not to be taken on an empty stomach. The patients were recommended to leave 3-4 h between each meal/IMP dose.

    Number of subjects in period 1
    		EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Started
    52
    52
    52
    Completed
    44
    45
    46
    Not completed
    8
    7
    6
         Consent withdrawn by subject
    3
    2
    5
         Adverse event, non-fatal
    4
    5
    -
         Lost to follow-up
    1
    -
    -
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    EMP16-02 - 120/40
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02 -120/40 (120 mg orlistat/40 mg acarbose).

    Reporting group title
    EMP16-02 - 150/50
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02-150/50 (150 mg orlistat/50 mg acarbose).

    Reporting group title
    Placebo
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive placebo.

    Reporting group values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo Total
    Number of subjects
    		 52 52 52 156
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.4 ± 12.2 50.7 ± 13.6 49.5 ± 12.8 -
    Gender categorical
    Units: Subjects
        Female
    		 38 36 37 111
        Male
    		 14 16 15 45
    Body Mass Index (BMI)
    Units: (kg/m2)
        arithmetic mean (standard deviation)
    		 35.1 ± 3.3 34.6 ± 3.6 36.2 ± 4.5 -

    End points

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    End points reporting groups
    Reporting group title
    EMP16-02 - 120/40
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02 -120/40 (120 mg orlistat/40 mg acarbose).

    Reporting group title
    EMP16-02 - 150/50
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02-150/50 (150 mg orlistat/50 mg acarbose).

    Reporting group title
    Placebo
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive placebo.

    Primary: Relative (%) change from baseline in body weight after 26 weeks

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    End point title
    		 Relative (%) change from baseline in body weight after 26 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. This end-point reports the mean relative (%) change from baseline (Visit 2, pre-dose) in body weight at Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Primary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: percent
    arithmetic mean (standard deviation)
        Visit 5 (week 26), pre-dose
    -5.8 ± 5.3
    -6.5 ± 4.4
    -0.7 ± 3.7
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    Relative (%) change from baseline in body weight after 26 weeks of treatment with EMP16-02 (120 mg O/40 mg A) as compared to placebo was analysed using analysis of variance with treatment as the independent variable. Hypothesis testing was two-sided. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 ANOVA
    Confidence interval
    Notes
    [1] - Hypothesis testing used a 5% significance level (α=0.05).
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    Relative (%) change from baseline in body weight after 26 weeks of treatment with EMP16-02 (150 mg O/50 mg A) as compared to placebo was analysed using analysis of variance with treatment as the independent variable. Hypothesis testing was two-sided. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval

    Secondary: Absolute change from baseline in body weight after 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in body weight after 14 and 26 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. This end-point reports the mean absolute change from baseline (Visit 2, pre-dose) in body weight at Week 14 and Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45 [2]
    47 [3]
    49 [4]
    Units: kg
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -4.29 ± 3.19
    -4.83 ± 3.11
    -1.18 ± 3.30
        Visit 5 (week 26), pre-dose
    -5.75 ± 5.35
    -6.44 ± 4.59
    -0.78 ± 3.75
    Notes
    [2] - n=45 for Visit 4 and n=44 for Visit 5
    [3] - n=47 for visit 4 and n=45 for Visit 5
    [4] - n=49 for Visit 4 and n=46 for Visit 5
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14 & Week 26
    Statistical analysis description
    Absolute change from baseline in body weight was analysed using the ANCOVA model, with treatment as independent variable and weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 for Week 14 and 90 for Week 26.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [5]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [5] - This p-value applies for both Week 14 and Week 26.
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14 & Week 26
    Statistical analysis description
    Absolute change from baseline in body weight was analysed using the ANCOVA model, with treatment as independent variable and weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 96 for Week 14 and 91 for Week 26.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [6]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [6] - This p-value applies for both Week 14 and Week 26.

    Secondary: Relative (%) change from baseline in body weight after 14 weeks

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    End point title
    		 Relative (%) change from baseline in body weight after 14 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. This end-point reports the mean relative (%) change from baseline (Visit 2, pre-dose) at Week 14. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7) and Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: percent
    arithmetic mean (standard deviation)
        Visit 4 (Week 14), pre-dose
    -4.4 ± 3.1
    -4.8 ± 2.9
    -1.1 ± 3.1
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    Relative (%) change from baseline in body weight after 14 weeks of treatment with EMP16-02 (120 mg O/40 mg A) as compared to placebo was analysed using analysis of variance with treatment as the independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    Placebo v EMP16-02 - 120/40
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    Relative (%) change from baseline in body weight after 14 weeks of treatment with EMP16-02 (150 mg O/50 mg A) as compared to placebo was analysed using analysis of variance with treatment as the independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval

    Secondary: Proportion of patients with ≥5% and ≥10% decrease in body weight compared to baseline after 14 weeks

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    End point title
    		 Proportion of patients with ≥5% and ≥10% decrease in body weight compared to baseline after 14 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. This end-point reports the proportions (%) of patients with ≥5% and ≥10% decrease in body weight relative to baseline (Visit 2, pre-dose) at Week 14. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7) and Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: percent
    number (not applicable)
        ≥5% decrease - Visit 4 (week 14), pre-dose
    31
    43
    14
        ≥10% decrease - Visit 4 (week 14), pre-dose
    8.9
    4.3
    0
    Statistical analysis title
    		 EMP16-02-120/40 VS placebo - ≥5% decrease -Week 14
    Statistical analysis description
    The proportion of patients with ≥5% decrease in body weight compared to baseline after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0504
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02-150/50 VS placebo - ≥5% decrease -Week 14
    Statistical analysis description
    The proportion of patients with ≥5% decrease in body weight compared to baseline after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0021
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02-120/40 VS placebo- ≥10% decrease -Week 14
    Statistical analysis description
    The proportion of patients with ≥10% decrease in body weight compared to baseline after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    Placebo v EMP16-02 - 120/40
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0329
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02-150/50 VS placebo- ≥10% decrease -Week 14
    Statistical analysis description
    The proportion of patients with ≥10% decrease in body weight compared to baseline after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1445
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Proportion of patients with ≥5% and ≥10% decrease in body weight compared to baseline after 26 weeks

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    End point title
    		 Proportion of patients with ≥5% and ≥10% decrease in body weight compared to baseline after 26 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. This end-point reports the proportions (%) of patients with ≥5% and ≥10% decrease in body weight relative to baseline (Visit 2, pre-dose) at Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: percent
    number (not applicable)
        ≥5% decrease - Visit 5 (week 26), pre-dose
    55
    67
    13
        ≥10% decrease - Visit 5 (week 26), pre-dose
    23
    22
    2.2
    Statistical analysis title
    		 EMP16-02-120/40 VS placebo - ≥5% decrease -Week 26
    Statistical analysis description
    The proportion of patients with ≥5% decrease in body weight compared to baseline after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02-150/50 VS placebo - ≥5% decrease -Week 26
    Statistical analysis description
    The proportion of patients with ≥5% decrease in body weight compared to baseline after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02-120/40 VS placebo- ≥10% decrease -Week 26
    Statistical analysis description
    The proportion of patients with ≥10% decrease in body weight compared to baseline after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0029
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02-150/50 VS placebo- ≥10% decrease -Week 26
    Statistical analysis description
    The proportion of patients with ≥10% decrease in body weight compared to baseline after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0034
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Relative (%) change from baseline in BMI after 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in BMI after 14 and 26 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. Height was measured in cm (no decimals) without shoes at screening (Visit 1). BMI was calculated based on the height measured at Visit 1 and the weight measured at each visit analyzed. This end-point reports the mean relative (%) change in BMI from baseline (Visit 2, pre-dose) at Week 14 and Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26). Height was measured at Visit 1 Screening.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45 [7]
    47 [8]
    49 [9]
    Units: percent
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -4.4 ± 3.1
    -4.8 ± 3.0
    -1.0 ± 3.1
        Visit 5 (Week 26), pre-dose
    -5.8 ± 5.3
    -6.5 ± 4.4
    -0.7 ± 3.7
    Notes
    [7] - n=45 for Visit 4 and n=44 for Visit 5
    [8] - n=47 for Visit 4 and n=45 for Visit 5
    [9] - n=49 for Visit 4 and n=46 for Visit 5
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14 & Week 26
    Statistical analysis description
    The relative change from baseline in BMI after 14 and 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 and 90 for weeks 14 and 26 respectively.
    Comparison groups
    Placebo v EMP16-02 - 120/40
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [10]
    Method
    		 ANOVA
    Confidence interval
    Notes
    [10] - This p-value applies to both Week 14 and Week 26.
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14 & Week 26
    Statistical analysis description
    The relative change from baseline in BMI after 14 and 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 96 and 91 for weeks 14 and 26 respectively.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [11]
    Method
    		 ANOVA
    Confidence interval
    Notes
    [11] - This p-value applies to both Week 14 and Week 26.

    Secondary: Absolute change from baseline in BMI after 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in BMI after 14 and 26 weeks
    End point description
    Weight was measured in kg (one decimal) without shoes and without thick clothes such as jumpers at pre-specified visits. Height was measured in cm (no decimals) without shoes at screening (Visit 1). BMI was calculated based on the height measured at Visit 1 and the weight measured at each visit analyzed. This end-point reports the mean absolute change in BMI from baseline (Visit 2, pre-dose) at Week 14 and Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Weight was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26). Height was measured at Visit 1 Screening.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45 [12]
    47 [13]
    49 [14]
    Units: kg/m2
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -1.55 ± 1.18
    -1.67 ± 1.08
    -0.40 ± 1.17
        Visit 5 (Week 26), pre-dose
    -2.08 ± 1.99
    -2.23 ± 1.57
    -0.25 ± 1.33
    Notes
    [12] - n=45 for Visit 4 and n=44 for Visit 5
    [13] - n=47 for Visit 4 and n=45 for Visit 5
    [14] - n=49 for Visit 4 and n=46 for Visit 5
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14 & 26
    Statistical analysis description
    The absolute change from baseline in BMI after 14 and 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subject included in the analyses were 94 and 90 for Week 14 and Week 26 respectively.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [15]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [15] - This p-value applies to both Week 14 and 26.
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14 & 26
    Statistical analysis description
    The absolute change from baseline in BMI after 14 and 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subject included in the analyses were 96 and 91 for Week 14 and Week 26 respectively.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [16]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [16] - This p-value applies to both Week 14 and 26.

    Secondary: Absolute change from baseline in waist circumference after 14 weeks

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    End point title
    		 Absolute change from baseline in waist circumference after 14 weeks
    End point description
    Waist circumference was measured in cm (one decimal) at pre-specified visits. Thi end-point reports the mean absolute change from baseline (Visit 2, Day 1) in waist circumference at Week 14. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Waist circumference was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7) and Visit 4 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    46
    48
    Units: centimetre
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -3.92 ± 6.02
    -3.83 ± 4.11
    -3.22 ± 4.67
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - week 14
    Statistical analysis description
    The absolute change from baseline in waist circumference after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5054
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in waist circumference after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5552
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in waist circumference after 26 weeks

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    End point title
    		 Absolute change from baseline in waist circumference after 26 weeks
    End point description
    Waist circumference was measured in cm (one decimal) at pre-specified visits. This end-point reports the mean absolute change from baseline (Visit 2, Day 1) in waist circumference at Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Waist circumference was assessed at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26) .
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    44
    45
    Units: centimetre
    arithmetic mean (standard deviation)
        Visit 5 (Week 26), pre-dose
    -6.61 ± 5.67
    -6.80 ± 5.52
    -3.36 ± 5.36
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in waist circumference after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0087
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in waist circumference after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0047
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in sagittal diameter after 14 weeks

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    End point title
    		 Absolute change from baseline in sagittal diameter after 14 weeks
    End point description
    Sagittal diameter was measured in cm (one decimal) at pre-specified visits. For measurement of the sagittal diameter, the patient lied down on his/her back while having knees bent, so that the lower back was in contact with the surface he/she was lying on. The distance from the back to the highest point of the abdomen was measured in cm while the patient exhaled. This end-point reports the mean absolute change from baseline (Visit 2, Day 1) in sagittal diameter at week 14. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Sagittal abdominal diameter was assessed at Visit 2 (Day 1) and Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: centimetre
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -1.79 ± 2.02
    -1.71 ± 2.16
    -0.75 ± 1.85
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in sagittal diameter after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0075
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in sagittal diameter after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0142
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in sagittal diameter after 26 weeks

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    End point title
    		 Absolute change from baseline in sagittal diameter after 26 weeks
    End point description
    Sagittal diameter was measured in cm (one decimal) at pre-specified visits. For measurement of the sagittal diameter, the patient lied down on his/her back while having knees bent, so that the lower back was in contact with the surface he/she was lying on. The distance from the back to the highest point of the abdomen was measured in cm while the patient exhaled. This end-point reports the mean absolute change from baseline (Visit 2, Day 1) in sagittal diameter at Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Sagittal abdominal diameter was assessed at Visit 2 (Day 1), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: centimetre
    arithmetic mean (standard deviation)
        Visit 5 (Week 26), pre-dose
    -1.35 ± 2.22
    -1.89 ± 2.06
    -0.49 ± 2.13
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in sagittal diameter after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0522
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in sagittal diameter after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in percentage body fat after 14 weeks

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    End point title
    		 Relative (%) change from baseline in percentage body fat after 14 weeks
    End point description
    Body composition (percentage body fat) was measured using a bio-impedance measuring device (Tanita BC-545N), according to the manufacturer’s instructions, at pre-specified visits during the study. This end-point reports the mean relative (%) change from baseline (Visit 2, Day 1) in percentage body fat after 14 weeks. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Percentage body fat was assessed at Visit 2 (Day 1) and Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    47
    49
    Units: percent
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -0.4 ± 9.1
    -2.8 ± 6.2
    0.5 ± 5.8
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in percentage body fat after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3682
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in percentage body fat after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0233
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in percentage body fat after 26 weeks

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    End point title
    		 Relative (%) change from baseline in percentage body fat after 26 weeks
    End point description
    Body composition (percentage body fat) was measured using a bio-impedance measuring device (Tanita BC-545N), according to the manufacturer’s instructions, at pre-specified visits during the study. This end-point reports the mean relative (%) change from baseline (Visit 2, Day 1) in percentage body fat after 26 weeks. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Percentage body fat was assessed at Visit 2 (Day 1) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: percent
    arithmetic mean (standard deviation)
        Visit 5 (Week 26), pre-dose
    -2.8 ± 10.2
    -5.4 ± 7.4
    -0.3 ± 7.8
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in percentage body fat after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1733
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in percentage body fat after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0047
    Method
    		 ANOVA
    Confidence interval

    Secondary: Absolute change from baseline in percentage body fat after 14 weeks

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    End point title
    		 Absolute change from baseline in percentage body fat after 14 weeks
    End point description
    Body composition (percentage body fat) was measured using a bio-impedance measuring device (Tanita BC-545N), according to the manufacturer’s instructions, at pre-specified visits during the study. This end-point reports the mean absolute change from baseline (Visit 2, Day 1) in percentage body fat after 14 weeks. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Percentage body fat was assessed at Visit 2 (Day 1) and Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    47
    49
    Units: percent
    arithmetic mean (standard deviation)
        Visit 4 (week 14), pre-dose
    -0.40 ± 3.33
    -1.11 ± 2.24
    0.15 ± 2.40
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in percentage of body fat after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2727
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in percentage of body fat after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0195
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in percentage body fat after 26 weeks

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    End point title
    		 Absolute change from baseline in percentage body fat after 26 weeks
    End point description
    Body composition (percentage body fat) was measured using a bio-impedance measuring device (Tanita BC-545N), according to the manufacturer’s instructions, at pre-specified visits during the study. This end-point reports the mean absolute change from baseline (Visit 2, Day 1) in percentage body fat after 26 weeks. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Percentage body fat was assessed at Visit 2 (Day 1) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: percent
    arithmetic mean (standard deviation)
        Visit 5 (Week 26), pre-dose
    -1.45 ± 3.73
    -2.21 ± 2.68
    -0.19 ± 3.13
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in percentage of body fat after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0676
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in percentage of body fat after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0035
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Relative change from baseline in satiety and craving after 14 weeks

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    End point title
    		 Relative change from baseline in satiety and craving after 14 weeks
    End point description
    The satiety and craving questionnaire consists of 7 questions about sense of hunger, sense of satiety and craving for certain types of food that need to be answered on a scale from 0 (not at all) to 9 (extremely much). At each applicable visit, the patients answered the questionnaire once prior to breakfast and 4 times after breakfast (once every hour). The total score of all questionnaires were combined in descriptive summaries. A low score indicates low appetite while a high score indicates high appetite. This end-point reports the mean relative (%) change from baseline (Visit 2, Day 1) in total score at week 14. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    The satiety and craving questionnaires were filled in by the patients at Visit 2 (Day1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26). The questionnaires were fillid in before breakfast, then every hour for 4 hours until lunch.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    38
    37
    35
    Units: percent
    arithmetic mean (standard deviation)
        Visit 4 (week 14)
    3.2 ± 34.6
    1.5 ± 27.9
    -1.1 ± 34.1
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The Satiety and craving questionnaire includes 7 questions, with a scale 0 (not at all) to 9 (extremely much). The second and third question in the questionnaire were reversed before calculating the total score. Satiety and craving as total score after 14 weeks of treatment with EMP16-120/40 as compared to placebo, corrected for hunger and craving after standardised breakfast at baseline, was analyzed using the Wilcoxon Rank Sum test.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6389
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The Satiety and craving questionnaire includes 7 questions, with a scale 0 (not at all) to 9 (extremely much). The second and third question in the questionnaire were reversed before calculating the total score. Satiety and craving as total score after 14 weeks of treatment with EMP16-150/50 as compared to placebo, corrected for hunger and craving after standardised breakfast at baseline, was analyzed using the Wilcoxon Rank Sum test.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    72
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7017
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Relative change from baseline in satiety and craving after 26 weeks

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    End point title
    		 Relative change from baseline in satiety and craving after 26 weeks
    End point description
    The satiety and craving questionnaire consists of 7 questions about sense of hunger, sense of satiety and craving for certain types of food that need to be answered on a scale from 0 (not at all) to 9 (extremely much). At each applicable visit, the patients answered the questionnaire once prior to breakfast and 4 times after breakfast (once every hour). The total score of all questionnaires were combined in descriptive summaries. A low score indicates low appetite while a high score indicates high appetite. This end-point reports the mean relative (%) change from baseline (Visit 2, Day 1) in total score at week 14. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    The satiety and craving questionnaires were filled in by the patients at Visit 2 (Day1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26). The questionnaires were fillid in before breakfast, then every hour for 4 hours until lunch.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    35
    34
    38
    Units: percent
    arithmetic mean (standard deviation)
        Visit 5 (Week 26)
    12.7 ± 40.3
    3.6 ± 34.0
    3.3 ± 37.7
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The Satiety and craving questionnaire includes 7 questions, with a scale 0 (not at all) to 9 (extremely much). The second and third question in the questionnaire were reversed before calculating the total score. Satiety and craving as total score after 26 weeks of treatment with EMP16-120/40 as compared to placebo, corrected for hunger and craving after standardised breakfast at baseline, was analyzed using the Wilcoxon Rank Sum test.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1762
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The Satiety and craving questionnaire includes 7 questions, with a scale 0 (not at all) to 9 (extremely much). The second and third question in the questionnaire were reversed before calculating the total score. Satiety and craving as total score after 26 weeks of treatment with EMP16-150/50 as compared to placebo, corrected for hunger and craving after standardised breakfast at baseline, was analyzed using the Wilcoxon Rank Sum test.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    72
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9057
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting albumin after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting albumin after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting albumin after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [17]
    50 [18]
    50 [19]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    1.4 ± 7.4
    1.9 ± 7.2
    -0.5 ± 6.3
        VISIT 4 (WEEK 14), PREDOSE
    -1.3 ± 4.5
    -2.2 ± 7.2
    -3.5 ± 5.3
        VISIT 5 (WEEK 26), PREDOSE
    -0.3 ± 5.8
    -0.4 ± 7.2
    -0.8 ± 6.0
    Notes
    [17] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [18] - n=50 for week 7, n=47 for week 14 and n=45 for week 26
    [19] - n=50 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting albumin after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1787
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting albumin after 7 weeks of treatment with or EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0897
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting albumin after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0447
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting albumin after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1122
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting albumin after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3186
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting albumin after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3509
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting glucose after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting glucose after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting glucose after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [20]
    50 [21]
    50 [22]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -2.3 ± 7.2
    -2.5 ± 9.9
    -1.4 ± 6.2
        VISIT 4 (WEEK 14), PREDOSE
    -4.5 ± 7.9
    -4.2 ± 8.9
    -2.4 ± 6.6
        VISIT 5 (WEEK 26), PREDOSE
    -4.2 ± 8.2
    -4.1 ± 10.4
    -2.4 ± 7.6
    Notes
    [20] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [21] - n=50 for week 7, n=47 for week 14 and n=45 for week 26
    [22] - n=50 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting glucose after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5665
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting glucose after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4785
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting glucose after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.208
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting glucose after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2512
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting glucose after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4333
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting glucose after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4537
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting hemoglobin A1C (HbA1c) after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting hemoglobin A1C (HbA1c) after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting hemoglobin A1C (HbA1c) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [23]
    50 [24]
    50 [25]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -3.9 ± 5.7
    -2.5 ± 4.6
    -1.7 ± 3.9
        VISIT 4 (WEEK 14), PREDOSE
    -2.1 ± 5.5
    -0.6 ± 5.3
    0.2 ± 5.3
        VISIT 5 (WEEK 26), PREDOSE
    -3.1 ± 5.8
    -2.8 ± 6.1
    -1.5 ± 5.8
    Notes
    [23] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [24] - n=50 for week 7, n=47 for week 14 and n=45 for week 26
    [25] - n=50 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting HbA1c after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.022
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting HbA1c after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3992
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting HbA1c after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0252
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting HbA1c after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3543
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting HbA1c after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0753
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting HbA1c after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1711
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting insulin after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting insulin after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting insulin after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [26]
    49 [27]
    50 [28]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -15.0 ± 29.7
    -13.6 ± 37.4
    -8.0 ± 33.2
        VISIT 4 (WEEK 14), PREDOSE
    -15.9 ± 32.1
    -13.7 ± 39.1
    5.1 ± 49.6
        VISIT 5 (WEEK 26), PREDOSE
    -9.1 ± 35.8
    7.5 ± 106.9
    0.6 ± 48.8
    Notes
    [26] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [27] - n=49 for week 7, n=46 for week 14 and n=43 for week 26
    [28] - n=50 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting insulin after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3037
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting insulin after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4097
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting insulin after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0096
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting insulin after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 95 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0192
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting insulin after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4187
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting insulin after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7561
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting triglycerides after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting triglycerides after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting triglycerides after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [29]
    50 [30]
    49 [31]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    7.3 ± 32.8
    6.3 ± 41.0
    -3.6 ± 29.0
        VISIT 4 (WEEK 14), PREDOSE
    -2.5 ± 28.3
    1.2 ± 38.4
    -8.3 ± 36.2
        VISIT 5 (WEEK 26), PREDOSE
    2.4 ± 37.6
    5.0 ± 46.0
    -8.6 ± 28.3
    Notes
    [29] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [30] - n=50 for week 7, n=47 for week 14 and n=45 for week 26
    [31] - n=49 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting triglycerides after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1252
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting triglycerides after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1613
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting triglycerides after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 94 (the number 97 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6082
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting triglycerides after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 96 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1851
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting triglycerides after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 90 (the number 97 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.368
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting triglycerides after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 91 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.122
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting LDL cholesterol after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting LDL cholesterol after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting low-density lipoprotein (LDL) cholesterol after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [32]
    50 [33]
    50 [34]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -12.2 ± 13.0
    -9.5 ± 13.3
    0.1 ± 16.8
        VISIT 4 (WEEK 14), PREDOSE
    -13.8 ± 12.8
    -9.0 ± 19.5
    -3.1 ± 17.7
        VISIT 5 (WEEK 26), PREDOSE
    -8.8 ± 13.7
    -7.4 ± 15.3
    1.8 ± 18.5
    Notes
    [32] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [33] - n=50 for week 7, n=47 for week 14 and n=45 for week 26
    [34] - n=50 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting LDL cholesterol after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting LDL cholesterol after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0012
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting LDL cholesterol after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0038
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting LDL cholesterol after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.082
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting LDL cholesterol after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0017
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting LDL cholesterol after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0028
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting HDL cholesterol after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting HDL cholesterol after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting high-density lipoprotein (HDL) cholesterol after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [35]
    50 [36]
    50 [37]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -10.4 ± 10.4
    -11.2 ± 10.8
    2.5 ± 14.4
        VISIT 4 (WEEK 14), PREDOSE
    -9.8 ± 11.3
    -13.5 ± 11.4
    -0.8 ± 13.1
        VISIT 5 (WEEK 26), PREDOSE
    -7.6 ± 12.0
    -10.9 ± 12.3
    -0.3 ± 12.8
    Notes
    [35] - n=48 for week 7, n=45 for week 14 and n=44 for week 26
    [36] - n=50 for week 7, n=47 for week 14 and n=45 for week 26
    [37] - n=50 for week 7, n=49 for week 14 and n=46 for week 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting HDL cholesterol after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting HDL cholesterol after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting HDL cholesterol after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0005
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting HDL cholesterol after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting HDL cholesterol after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0038
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting HDL cholesterol after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in this analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting total cholesterol after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting total cholesterol after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting total cholesterol after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [38]
    50 [39]
    50 [40]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -9.4 ± 10.9
    -8.8 ± 10.2
    0.4 ± 10.1
        VISIT 4 (WEEK 14), PREDOSE
    -12.2 ± 10.5
    -9.7 ± 12.7
    -3.6 ± 11.1
        VISIT 5 (WEEK 26), PREDOSE
    -8.6 ± 11.4
    -8.0 ± 12.5
    -2.2 ± 11.3
    Notes
    [38] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [39] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [40] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting total cholesterol after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting total cholesterol after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting total cholesterol after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0003
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting total cholesterol after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0047
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting total cholesterol after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting total cholesterol after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0021
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting hs-CRP after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting hs-CRP after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting high-sensitivity C-reactive protein (hs-CRP) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [41]
    50 [42]
    50 [43]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    26.5 ± 200.5
    10.2 ± 91.7
    42.2 ± 321.7
        VISIT 4 (WEEK 14), PREDOSE
    -5.6 ± 60.5
    12.6 ± 134.3
    38.2 ± 241.1
        VISIT 5 (WEEK 26), PREDOSE
    7.2 ± 106.0
    -19.5 ± 37.0
    5.8 ± 65.8
    Notes
    [41] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [42] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [43] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting hs-CRP after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7314
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting hs-CRP after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4793
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting hs-CRP after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2511
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting hs-CRP after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.425
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting hs-CRP after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6908
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting hs-CRP after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0665
    Method
    		 ANOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting albumin after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting albumin after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting albumin after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [44]
    50 [45]
    50 [46]
    Units: g/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    0.5 ± 3.0
    0.6 ± 2.8
    -0.2 ± 2.5
        VISIT 4 (WEEK 14), PREDOSE
    -0.6 ± 1.9
    -1.0 ± 2.9
    -1.4 ± 2.1
        VISIT 5 (WEEK 26), PREDOSE
    -0.2 ± 2.4
    -0.2 ± 2.9
    -0.3 ± 2.4
    Notes
    [44] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [45] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [46] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting albumin after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1607
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting albumin after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1098
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting albumin after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0775
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting albumin after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3853
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting albumin after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9178
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting albumin after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9943
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting glucose after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting glucose after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting glucose after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [47]
    50 [48]
    50 [49]
    Units: mmol/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -0.16 ± 0.45
    -0.17 ± 0.63
    -0.10 ± 0.40
        VISIT 4 (WEEK 14), PREDOSE
    -0.30 ± 0.50
    -0.27 ± 0.55
    -0.15 ± 0.45
        VISIT 5 (WEEK 26), PREDOSE
    -0.27 ± 0.50
    -0.26 ± 0.65
    -0.16 ± 0.49
    Notes
    [47] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [48] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [49] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting glucose after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.478
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting glucose after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.426
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting glucose after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1858
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting glucose after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2475
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting glucose after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3422
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting glucose after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3651
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting hemoglobin A1C (HbA1c) after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting hemoglobin A1C (HbA1c) after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting hemoglobin A1C (HbA1c) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [50]
    50 [51]
    50 [52]
    Units: mmol/mol
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -1.5 ± 2.3
    -0.9 ± 1.7
    -0.7 ± 1.4
        VISIT 4 (WEEK 14), PREDOSE
    -0.9 ± 2.3
    -0.3 ± 1.9
    0.0 ± 1.9
        VISIT 5 (WEEK 26), PREDOSE
    -1.2 ± 2.3
    -1.1 ± 2.4
    -0.6 ± 2.2
    Notes
    [50] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [51] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [52] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting HbA1c after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0283
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting HbA1c after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5118
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting HbA1c after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects ncluded in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0667
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting HbA1c after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects ncluded in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5837
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting HbA1c after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects ncluded in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2908
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting HbA1c after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects ncluded in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3418
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting insulin after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting insulin after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting insulin after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [53]
    49 [54]
    50 [55]
    Units: mIU/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -3.958 ± 8.125
    -3.129 ± 8.642
    -3.320 ± 10.68
        VISIT 4 (WEEK 14), PREDOSE
    -4.222 ± 7.674
    -3.241 ± 7.919
    -0.01020 ± 11.83
        VISIT 5 (WEEK 26), PREDOSE
    -3.620 ± 9.705
    0.07907 ± 18.10
    -1.509 ± 8.411
    Notes
    [53] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [54] - n=49 for week 7, n=46 for week 14 and n=43 for week 26.
    [55] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting insulin after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6382
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting insulin after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9784
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting insulin after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in this analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0358
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting insulin after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in this analysis was 95 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1012
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting insulin after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in this analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3965
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting insulin after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in this analysis was 89 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5905
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting triglycerides after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting triglycerides after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting triglycerides after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [56]
    50 [57]
    49 [58]
    Units: mmol/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    0.011 ± 0.632
    -0.047 ± 0.619
    -0.149 ± 0.659
        VISIT 4 (WEEK 14), PREDOSE
    -0.116 ± 0.483
    -0.070 ± 0.623
    -0.275 ± 0.732
        VISIT 5 (WEEK 26), PREDOSE
    -0.092 ± 0.642
    -0.028 ± 0.626
    -0.237 ± 0.784
    Notes
    [56] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [57] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [58] - n=49 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting triglycerides after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2494
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting triglycerides after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4506
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting triglycerides after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 97 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3274
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting triglycerides after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 96 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1452
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting triglycerides after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 97 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    97
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4394
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting triglycerides after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 99 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1912
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting LDL cholesterol after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting LDL cholesterol after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting low-density lipoprotein (LDL) cholesterol after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [59]
    50 [60]
    50 [61]
    Units: mmol/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -0.49 ± 0.52
    -0.34 ± 0.52
    -0.05 ± 0.51
        VISIT 4 (WEEK 14), PREDOSE
    -0.51 ± 0.46
    -0.36 ± 0.66
    -0.14 ± 0.51
        VISIT 5 (WEEK 26), PREDOSE
    -0.34 ± 0.52
    -0.26 ± 0.61
    0.01 ± 0.55
    Notes
    [59] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [60] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [61] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting LDL cholesterol after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting LDL cholesterol after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0051
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting LDL cholesterol after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting LDL cholesterol after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0473
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting LDL cholesterol after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0024
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting LDL cholesterol after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0203
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting HDL cholesterol after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting HDL cholesterol after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting high-density lipoprotein (HDL) cholesterol after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [62]
    50 [63]
    50 [64]
    Units: mmol/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -0.15 ± 0.14
    -0.16 ± 0.16
    0.03 ± 0.19
        VISIT 4 (WEEK 14), PREDOSE
    -0.14 ± 0.15
    -0.20 ± 0.19
    -0.02 ± 0.19
        VISIT 5 (WEEK 26), PREDOSE
    -0.11 ± 0.16
    -0.16 ± 0.19
    -0.02 ± 0.18
    Notes
    [62] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [63] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [64] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting HDL cholesterol after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting HDL cholesterol after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting HDL cholesterol after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0015
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting HDL cholesterol after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting HDL cholesterol after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0253
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting HDL cholesterol after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting cholesterol after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting cholesterol after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting total cholesterol after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [65]
    50 [66]
    50 [67]
    Units: mmol/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -0.59 ± 0.82
    -0.48 ± 0.59
    0.00 ± 0.53
        VISIT 4 (WEEK 14), PREDOSE
    -0.72 ± 0.70
    -0.56 ± 0.76
    -0.22 ± 0.56
        VISIT 5 (WEEK 26), PREDOSE
    -0.53 ± 0.73
    -0.45 ± 0.76
    -0.13 ± 0.59
    Notes
    [65] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [66] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [67] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting total cholesterol after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting total cholesterol after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0005
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting total cholesterol after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting total cholesterol after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0142
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting total cholesterol after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0069
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting total cholesterol after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0297
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting hs-CRP after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting hs-CRP after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting high-sensitivity C-reactive protein (hs-CRP) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [68]
    50 [69]
    50 [70]
    Units: mg/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -0.7 ± 3.2
    0.1 ± 2.6
    -0.2 ± 7.5
        VISIT 4 (WEEK 14), PREDOSE
    -0.7 ± 3.1
    -0.7 ± 2.8
    -0.3 ± 7.3
        VISIT 5 (WEEK 26), PREDOSE
    0.7 ± 11.0
    -1.1 ± 2.0
    -0.6 ± 6.6
    Notes
    [68] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [69] - n=50 for week 7, n=47 for week 14 and n=45 for week 26.
    [70] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting hs-CRP after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7331
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting hs-CRP after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6953
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting hs-CRP after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8853
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting hs-CRP after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 96 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7778
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting hs-CRP after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3464
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting hs-CRP after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8254
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting ALT after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting ALT after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting alanine aminotransferase (ALT) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [71]
    50 [72]
    50 [73]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    10.8 ± 51.5
    8.0 ± 38.5
    -6.7 ± 27.6
        VISIT 4 (WEEK 14), PREDOSE
    3.0 ± 35.3
    17.6 ± 85.5
    -3.2 ± 55.6
        VISIT 5 (WEEK 26), PREDOSE
    -4.5 ± 36.9
    3.6 ± 49.6
    -7.7 ± 27.9
    Notes
    [71] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [72] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [73] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting ALT after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0333
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting ALT after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0707
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting ALT after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6289
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting ALT after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 95 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1126
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting ALT after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9673
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting ALT after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6607
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting AST after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting AST after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting aspartate aminotransferase (AST) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    47 [74]
    50 [75]
    48 [76]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    4.2 ± 28.7
    4.9 ± 26.1
    -2.7 ± 31.8
        VISIT 4 (WEEK 14), PREDOSE
    -4.5 ± 21.2
    22.5 ± 183.8
    -11.2 ± 22.2
        VISIT 5 (WEEK 26), PREDOSE
    -7.3 ± 22.2
    0.9 ± 34.4
    -4.5 ± 27.6
    Notes
    [74] - n=47 for week 7, n=44 for week 14 and n=43 for week 26.
    [75] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [76] - n=48 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting AST after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2479
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting AST after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1949
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting AST after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the anlaysis was 93 (the number 95 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7191
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting AST after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the anlaysis was 95 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1281
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting AST after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the anlaysis was 89 (the number 95 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8387
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting AST after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the anlaysis was 91 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3571
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting ALP after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting ALP after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting alkaline phosphatase (ALP) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [77]
    50 [78]
    50 [79]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    3.3 ± 10.4
    0.6 ± 10.7
    -0.8 ± 10.9
        VISIT 4 (WEEK 14), PREDOSE
    3.8 ± 10.7
    1.0 ± 13.8
    -0.9 ± 12.3
        VISIT 5 (WEEK 26), PREDOSE
    8.5 ± 14.9
    3.7 ± 15.1
    2.4 ± 11.4
    Notes
    [77] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [78] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [79] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting ALP after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0608
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting ALP after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5028
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting ALP after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0717
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting ALP after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 95 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3449
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting ALP after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0618
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting ALP after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.916
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in fasting GGT after 7, 14 and 26 weeks

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    End point title
    		 Relative (%) change from baseline in fasting GGT after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean relative (%) change from baseline in fasting gamma glutamyl transferase (GGT) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [80]
    50 [81]
    50 [82]
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -5.3 ± 21.1
    -6.1 ± 20.2
    -1.5 ± 28.3
        VISIT 4 (WEEK 14), PREDOSE
    -10.5 ± 41.6
    -2.0 ± 46.1
    -1.6 ± 44.0
        VISIT 5 (WEEK 26), PREDOSE
    -9.6 ± 38.2
    -12.2 ± 23.5
    -2.0 ± 31.7
    Notes
    [80] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [81] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [82] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting GGT after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4247
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The relative (%) change from baseline in fasting GGT after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3328
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting GGT after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3522
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in fasting GGT after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 95 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8695
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting GGT after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1313
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in fasting GGT after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0334
    Method
    		 ANOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting ALT after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting ALT after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting alanine aminotransferase (ALT) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [83]
    50 [84]
    50 [85]
    Units: ukat/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    0.024 ± 0.242
    0.020 ± 0.234
    -0.056 ± 0.188
        VISIT 4 (WEEK 14), PREDOSE
    -0.026 ± 0.204
    0.043 ± 0.366
    -0.063 ± 0.202
        VISIT 5 (WEEK 26), PREDOSE
    -0.057 ± 0.217
    -0.015 ± 0.313
    -0.069 ± 0.151
    Notes
    [83] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [84] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [85] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting ALT after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0735
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting ALT after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0878
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting ALT after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4925
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting ALT after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 95 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0555
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting ALT after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8744
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting ALT after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3057
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting AST after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting AST after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting aspartate aminotransferase (AST) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    47 [86]
    50 [87]
    48 [88]
    Units: ukat/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    0.010 ± 0.127
    0.011 ± 0.128
    -0.040 ± 0.150
        VISIT 4 (WEEK 14), PREDOSE
    -0.034 ± 0.105
    0.076 ± 0.721
    -0.072 ± 0.143
        VISIT 5 (WEEK 26), PREDOSE
    -0.046 ± 0.112
    -0.012 ± 0.138
    -0.037 ± 0.137
    Notes
    [86] - n=47 for week 7, n=44 for week 14 and n=43 for week 26.
    [87] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [88] - n=48 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting AST after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0915
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting AST after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0674
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting AST after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 93 (the number 95 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6081
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting AST after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 95 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0863
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting AST after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 89 (the number 95 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6796
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting AST after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3852
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting ALP after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting ALP after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting alkaline phosphatase (ALP) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [89]
    50 [90]
    50 [91]
    Units: ukat/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    0.031 ± 0.136
    -0.003 ± 0.128
    -0.016 ± 0.121
        VISIT 4 (WEEK 14), PREDOSE
    0.035 ± 0.135
    -0.001 ± 0.163
    -0.021 ± 0.141
        VISIT 5 (WEEK 26), PREDOSE
    0.090 ± 0.178
    0.036 ± 0.178
    0.013 ± 0.134
    Notes
    [89] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [90] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [91] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting ALP after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    Placebo v EMP16-02 - 120/40
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0675
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting ALP after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5983
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting ALP after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0823
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting ALP after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 95 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5335
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting ALP after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0367
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting ALP after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5585
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in fasting GGT after 7, 14 and 26 weeks

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    End point title
    		 Absolute change from baseline in fasting GGT after 7, 14 and 26 weeks
    End point description
    Venous blood samples (4 mL) were collected to analyze the fasting profile of lipid metabolism markers, glucose metabolism markers, and inflammation markers. All parameters were analyzed in immediate association with sampling. This end-point reports the mean absolute change from baseline in fasting gamma glutamyl transferase (GGT) after 7, 14 and 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis was done at Visit 2 (Day 1, baseline), Visit 3 (Week 7), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    48 [92]
    50 [93]
    50 [94]
    Units: ukat/L
    arithmetic mean (standard deviation)
        VISIT 3 (WEEK 7), PREDOSE
    -0.02958 ± 0.1519
    -0.04700 ± 0.1923
    -0.09420 ± 0.4697
        VISIT 4 (WEEK 14), PREDOSE
    -0.06933 ± 0.1948
    -0.01826 ± 0.2228
    -0.09367 ± 0.4742
        VISIT 5 (WEEK 26), PREDOSE
    -0.07318 ± 0.2006
    -0.07111 ± 0.1611
    -0.1226 ± 0.5147
    Notes
    [92] - n=48 for week 7, n=45 for week 14 and n=44 for week 26.
    [93] - n=50 for week 7, n=46 for week 14 and n=45 for week 26.
    [94] - n=50 for week 7, n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting GGT after 7 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.22
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in fasting GGT after 7 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3775
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting GGT after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 94 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6703
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in fasting GGT after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 95 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2478
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting GGT after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 98 refers to week 7).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4007
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in fasting GGT after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 91 (the number 100 refers to week 7).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.41
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Diabetic status at baseline, week 14 and week 26

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    End point title
    		 Diabetic status at baseline, week 14 and week 26
    End point description
    Diabetic status was defined as fasting glucose ≥ 7.0 mmol/L and prediabetic status was defined as fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L. This end-point reports the proportions (%) of diabetic, non-diabetic and prediabetic patients at baseline (Week 1, Day 1), Week 14 and Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood sampling for analysis of fasting glucose was done at Visit 2 (Day 1, baseline), Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52 [95]
    52 [96]
    52 [97]
    Units: percent
    number (not applicable)
        VISIT 2 (WEEK 1), PREDOSE - Diabetic
    9.6
    3.8
    9.6
        VISIT 2 (WEEK 1), PREDOSE - Non-diabetic
    65
    69
    54
        VISIT 2 (WEEK 1), PREDOSE - Prediabetic
    25
    27
    37
        VISIT 4 (WEEK 14), PREDOSE - Diabetic
    2.2
    4.3
    16
        VISIT 4 (WEEK 14), PREDOSE - Non-diabetic
    80
    81
    67
        VISIT 4 (WEEK 14), PREDOSE - Prediabetic
    18
    15
    16
        VISIT 5 (WEEK 26), PREDOSE - Diabetic
    4.5
    2.2
    13
        VISIT 5 (WEEK 26), PREDOSE - Non-diabetic
    75
    76
    65
        VISIT 5 (WEEK 26), PREDOSE - Prediabetic
    20
    22
    22
    Notes
    [95] - n=52 for Week 1 (baseline), n=45 for week 14 and n=44 for week 26.
    [96] - n=52 for Week 1 (baseline), n=47 for week 14 and n=45 for week 26.
    [97] - n=52 for Week 1 (baseline), n=49 for week 14 and n=46 for week 26.
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The change from baseline in the proportion of diabetic and prediabetic patients after 14 weeks of treatment with EMP16-02 as compared to placebo was analyzed using Chi-square test without continuity correction. The total number of subjects included in the analysis was 94 (the number 104 refers to Week 1).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0667
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The change from baseline in the proportion of diabetic and prediabetic patients after 14 weeks of treatment with EMP16-02 as compared to placebo was analyzed using Chi-square test without continuity correction. The total number of subjects included in the analysis was 96 (the number 104 refers to Week 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1368
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The change from baseline in the proportion of diabetic and prediabetic patients after 26 weeks of treatment with EMP16-02 as compared to placebo was analyzed using Chi-square test without continuity correction. The total number of subjects included in the analysis was 90 (the number 104 refers to Week 1).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3409
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The change from baseline in the proportion of diabetic and prediabetic patients after 26 weeks of treatment with EMP16-02 as compared to placebo was analyzed using Chi-square test without continuity correction. The total number of subjects included in the analysis was 91 (the number 104 refers to Week 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1488
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Relative (%) change from baseline in systolic blood pressure after 14 weeks

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    End point title
    		 Relative (%) change from baseline in systolic blood pressure after 14 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean relative (%) change from baseline in systolic blood pressure after 14 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 4 (WEEK 14), PRE-DOSE
    -1.9 ± 7.5
    -4.7 ± 9.5
    -1.4 ± 6.9
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in systolic and diastolic blood pressure, after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4224
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in systolic and diastolic blood pressure, after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0273
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in systolic blood pressure after 26 weeks

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    End point title
    		 Relative (%) change from baseline in systolic blood pressure after 26 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean relative (%) change from baseline in systolic blood pressure after 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 5 (WEEK 26), PRE-DOSE
    -1.7 ± 8.8
    -3.2 ± 9.2
    -1.1 ± 8.4
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in systolic blood pressure after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2631
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in systolic blood pressure after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0505
    Method
    		 ANOVA
    Confidence interval

    Secondary: Absolute change from baseline in systolic blood pressure after 14 weeks

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    End point title
    		 Absolute change from baseline in systolic blood pressure after 14 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean absolute change from baseline in systolic blood pressure after 14 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: mmHg
    arithmetic mean (standard deviation)
        VISIT 4 (WEEK 14), PRE-DOSE
    -2.6 ± 9.9
    -6.9 ± 13.4
    -2.2 ± 8.9
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in diastolic blood pressure after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7327
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in diastolic blood pressure after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in systolic blood pressure after 26 weeks

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    End point title
    		 Absolute change from baseline in systolic blood pressure after 26 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean absolute change from baseline in systolic blood pressure after 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: mmHg
    arithmetic mean (standard deviation)
        VISIT 5 (WEEK 26), PRE-DOSE
    -2.7 ± 12.0
    -4.9 ± 13.6
    -1.8 ± 11.2
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in systolic blood pressure after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5771
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in systolic blood pressure after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1822
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in diastolic blood pressure after 14 weeks

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    End point title
    		 Relative (%) change from baseline in diastolic blood pressure after 14 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean relative (%) change from baseline in diastolic blood pressure after 14 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 4 (WEEK 14), PRE-DOSE
    -3.2 ± 8.2
    -3.3 ± 10.1
    0.6 ± 7.1
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in diastolic blood pressure after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0215
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The relative (%) change from baseline in diastolic blood pressure after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0284
    Method
    		 ANOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in diastolic blood pressure after 26 weeks

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    End point title
    		 Relative (%) change from baseline in diastolic blood pressure after 26 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean relative (%) change from baseline in diastolic blood pressure after 26 weeks of treatment. 2 The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: percent
    arithmetic mean (standard deviation)
        VISIT 5 (WEEK 26), PRE-DOSE
    -3.3 ± 8.1
    -2.8 ± 9.3
    -1.4 ± 8.7
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in diastolic blood pressure after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1509
    Method
    		 ANOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The relative (%) change from baseline in diastolic blood pressure after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANOVA with treatment as independent variable. Data underlying the ANOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    Placebo v EMP16-02 - 150/50
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.148
    Method
    		 ANOVA
    Confidence interval

    Secondary: Absolute change from baseline in diastolic blood pressure after 14 weeks

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    End point title
    		 Absolute change from baseline in diastolic blood pressure after 14 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean absolute change from baseline in diastolic blood pressure after 14 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 4 (Week 14).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    47
    49
    Units: mmHg
    arithmetic mean (standard deviation)
        VISIT 4 (WEEK 14), PRE-DOSE
    -2.8 ± 7.0
    -3.3 ± 8.7
    0.2 ± 5.9
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in diastolic blood pressure after 14 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0542
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in diastolic blood pressure after 14 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0221
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Absolute change from baseline in diastolic blood pressure after 26 weeks

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    End point title
    		 Absolute change from baseline in diastolic blood pressure after 26 weeks
    End point description
    Systolic and diastolic blood pressure were measured in supine position after 10 minutes of rest. This end-point reports the mean absolute change from baseline in diastolic blood pressure after 26 weeks of treatment. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Blood pressure was assessed at Visit 2 (Day 1, baseline) and at Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44
    45
    46
    Units: mmHg
    arithmetic mean (standard deviation)
        VISIT 5 (WEEK 26), PRE-DOSE
    -3.0 ± 7.0
    -3.0 ± 8.1
    -1.5 ± 7.3
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in diastolic blood pressure after 26 weeks of treatment with EMP16-120/40 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3769
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in diastolic blood pressure after 26 weeks of treatment with EMP16-150/50 as compared to placebo was analyzed using ANCOVA with treatment as independent variable and body weight at baseline as covariates. Data underlying the ANCOVA has been imputated in case of missing values using Last Observation Carried Forward, LOCF.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.384
    Method
    		 ANCOVA
    Confidence interval

    Secondary: Relative (%) change from baseline in quality of life after 26 weeks

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    End point title
    		 Relative (%) change from baseline in quality of life after 26 weeks
    End point description
    The RAND-36 health questionnaire comprises 36 questions. The questionnaire taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perception. It also includes a single item that provides an indication of perceived change in health. A low score indicates poor healthrelated quality of life while a high score indicates good health-related quality of life. This end-point reports the mean relative (%) change from baseline (Week 1, Day 1) in score mean for the 8 health concepts scales and for the additional "Health Transition Score" included in the questionnaire, at week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    The RAND-36 health questionnaire was filled in by the subjects at Visit 2 (Day 1, baseline) and at Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    42 [98]
    41 [99]
    47 [100]
    Units: percent
    arithmetic mean (standard deviation)
        1. Physical functioning Mean - Week 26
    30.1 ± 110.8
    22.5 ± 38.2
    3.8 ± 17.7
        2. Role functioning/Physical Mean - Week 26
    19.4 ± 75.7
    35.4 ± 93.4
    6.9 ± 59.5
        3. Pain (Bodily Pain) Mean -Week 26
    5.6 ± 30.1
    23.4 ± 44.1
    2.8 ± 34.1
        4. General health Mean -Week 26
    12.6 ± 48.5
    10.8 ± 21.4
    -5.2 ± 19.8
        5. Energy/fatigue (Vitality) Mean - Week 26
    21.8 ± 114.2
    33.0 ± 102.3
    -3.0 ± 28.0
        6. Social Functioning Mean - Week 26
    5.0 ± 31.6
    28.2 ± 90.3
    0.7 ± 25.9
        7. Role functioning/Emotional Mean - Week 26
    -4.7 ± 47.0
    10.1 ± 76.6
    -13.7 ± 35.8
        8. Emotional wellbeing (Mental) Mean - Week 26
    -0.8 ± 29.0
    5.9 ± 34.4
    -4.9 ± 15.1
        9. Health Transition score Mean - Week 26
    41.3 ± 63.3
    48.4 ± 65.2
    13.0 ± 36.5
    Notes
    [98] - n=42 for scale no 1, 3-6 & 8 n=39 for scale no 2 & 7 n=40 for scale no 9
    [99] - n=41 for scale no 1 n=40 for scale no 2 & 9 n=41 for scale no 3-6 & 8 n=38 for scale no 7
    [100] - n=47 for scale no 1, 3, 4, 6 & 8 n=46 for scale no 2, 5 & 9 n=45 for scale no 7
    Statistical analysis title
    		 Scale no 1 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 1 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0131
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 1 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 1 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0024
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 2 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 2 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 85 (the number 89 refers to scale no 1).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2972
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 2 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 2 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 86 (the number 88 refers to scale no 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0923
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 3 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 3 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8938
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 3 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 3 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 88 (the number 89 refers to scale no 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0278
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 4 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 4 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.018
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 4 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 4 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0006
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 5 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 5 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 88 (the number 89 refers to scale no 1).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4296
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 5 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 5 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 87 (the number 88 refers to scale no 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0287
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 6 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 6 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5647
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 6 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 6 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0933
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 7 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 7 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 84 (the number 89 refers to scale no 1).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3628
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 7 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 7 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 83 (the number 88 refers to scale no 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2153
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 8 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 8 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2484
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 8 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 8 of the RAND-36 questionnaire.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.039
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 9 - EMP16-120/40 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 9 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 86 (the number 89 refers to scale no 1).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0138
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Statistical analysis title
    		 Scale no 9 - EMP16-150/50 VS placebo
    Statistical analysis description
    The RAND-36 QoL questionnaire was analyzed in accordance with the manual. Between groups p-value (Wilcoxon) was compared between EMP16-02 and placebo. This statistical analysis regards scale no 9 of the RAND-36 questionnaire. The total number of subjects included in the analysis was 87 (the number 88 refers to scale no 1).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    88
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0057
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Overall drop-out rate - Week 28

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    End point title
    		 Overall drop-out rate - Week 28
    End point description
    This end-point reports the cumulative overall drop-out rate (rate of early discontinuations) at the Safety follow-up Visit (Week 28). Subjects who missed one or several visits and who later re-entered the study were not considered drop-outs until they missed all remaining visits. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Collection of reasons for early discontinuations was done from Visit 1 Screening to Visit 6 (Week 28).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52
    52
    52
    Units: percent
    number (not applicable)
        Withdrawal overall - Week 28
    15.4
    13.5
    11.5
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 28
    Statistical analysis description
    The overall drop-out rate following treatment with EMP16-02 as compared to placebo was analyzed using Chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5656
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 28
    Statistical analysis description
    The overall drop-out rate following treatment with EMP16-02 as compared to placebo was analyzed using Chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7668
    Method
    		 Chi-squared
    Confidence interval

    Secondary: GI related drop-out rate - Week 28

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    End point title
    		 GI related drop-out rate - Week 28
    End point description
    This end-point reports the cumulative gastrointestinal (GI) related drop-out rate (rate of early discontinuations) at the Safety follow-up Visit (Week 28). Subjects who missed one or several visits and who later re-entered the study were not considered drop-outs until they missed all remaining visits. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Collection of reasons for early discontinuations was done from Visit 1 Screening to Visit 6 (Week 28).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52
    52
    52
    Units: percent
    number (not applicable)
        GI related withdrawal - Week 28
    7.7
    9.6
    0.0
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 28
    Statistical analysis description
    The GI related drop-out rate following treatment with EMP16-120/40 as compared to placebo was analyzed using Chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0414
    Method
    		 Chi-squared
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 28
    Statistical analysis description
    The GI related drop-out rate following treatment with EMP16-150/50 as compared to placebo was analyzed using Chi-square test without continuity correction.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0219
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Frequency, seriousness, severity and causality of adverse events (AEs)

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    End point title
    		 Frequency, seriousness, severity and causality of adverse events (AEs)
    End point description
    This end-point reports frequency, seriousness, severity and causality of adverse events (AEs) and serious AEs (SAEs). The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly or probably related to the IMP. GI symptoms were recorded using the Gastrointestinal symptom rating scale (GSRS) questionnaire. Only symptoms assessed by the Investigator as severe (either spontaneously reported or reported in the GSRS questionnaire) were recorded as AEs unless the GI symptom led to an early withdrawal. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    AEs (including serious AEs [SAEs]) were collected from the start of IMP administration until the end-of-study visit of each part.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52
    52
    52
    Units: Number of subjects
        Any AE
    32
    39
    30
        Any SAE
    0
    0
    0
        Any AE leading to withdrawal
    4
    6
    0
        Any AE leading to withdrawal of study drug
    4
    6
    0
        Any AE leading to death
    0
    0
    0
        Causality - Unlikely related
    22
    28
    27
        Causality - Possibly related
    7
    9
    6
        Causality - Probably related
    13
    12
    2
        Severity - Mild
    21
    24
    22
        Severity - Moderate
    11
    13
    11
        Severity - Severe
    14
    12
    3
        Severity - Life-threatening
    0
    0
    0
        Severity - Death
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Clinically significant (CS) abnormal findings in vital signs

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    End point title
    		 Clinically significant (CS) abnormal findings in vital signs
    End point description
    Systolic and diastolic blood pressure (BP) and pulse were measured in supine position after 10 minutes of rest. Vital signs were judged as normal, abnormal but not clinically significant (NCS) or abnormal and clinically significant (CS). Overall, there were no clinically relevant changes in mean systolic and diastolic BP between baseline and week 7, 14 and 26, respectively, in any treatment group. Similarly, there were no clinically relevant changes in mean pulse between the corresponding time points in any treatment group. This end-point reports CS abnormal findings in systolic & diastolic BP and pulse.
    End point type
    Secondary
    End point timeframe
    Vital signs were assessed at Visit 1 Screening, Visit 2 (Baseline), Visit 3 (Week 7), Visit 4 (Week 14), Visit 5 (Week 26) and Visit 6 (Week 28).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52
    52
    52
    Units: Number of abnormal CS findings
        CS abnormal findings in pulse
    0
    0
    0
        CS abnormal findings in blood pressure
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Abnormal Clinically Significant findings in ECG

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    End point title
    		 Abnormal Clinically Significant findings in ECG
    End point description
    Single 12-lead ECGs were recorded in supine position after 10 minutes of rest using an ECG machine. Safety ECGs were reviewed and interpreted on-site by the Investigator. Any abnormalities were specified and documented in the eCRF as clinically significant (CS) or not clinically significant (NCS). All ECGs were interpreted as normal or abnormal NCS by the Investigator at screening, week 28 or at early discontinuation end-of-study visits. There were no clinically relevant changes from baseline and no obvious differences between the treatment groups in terms of overall ECG evaluations and individual ECG parameters. One patient in the EMP16-120/40 group reported intermittent palpitations assessed as mild and unlikely related to treatment with the IMP by the Investigator. The occurrences started almost 3 months after the first dose and lasted over a period of 26 days. The ECG of the patient was interpreted as normal both at screening and at week 28.
    End point type
    Secondary
    End point timeframe
    ECG assessment was performed at Visit 1 Screening and at Visit 6 Safety follow-up (Week 28), or at early discontinuation end-of-study visits.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52 [101]
    52 [102]
    52 [103]
    Units: Number of abnormal CS findings
        Abnormal CS ECG findings - Screening
    0
    0
    0
        Abnormal CS ECG findings - Week 28
    0
    0
    0
        Abnormal CS ECG findings - End of Study
    0
    0
    0
    Notes
    [101] - n=52 for Screening Visit, n=44 for Week 28 and n=4 for End of study Visit
    [102] - n=52 for Screening Visit, n=45 for Week 28 and n=6 for End of study Visit
    [103] - n=52 for Screening Visit, n=45 for Week 28 and n=3 for End of study Visit
    No statistical analyses for this end point

    Secondary: Abnormal Clinically Significant findings in Clinical Chemistry

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    End point title
    		 Abnormal Clinically Significant findings in Clinical Chemistry
    End point description
    Blood samples for analysis of clinical chemistry parameters were collected through venipuncture and analyzed by routine analytical methods. The following parameters were analyzed: ALT, Albumin, ALP, AST, Bilirubin (total and conjugated), Calcium, Creatinine, GGT, Glucose, Hb1Ac, Phosphate, Potassium, Sodium and Urea. Parameter values were assessed as normal, abnormal but not clinically signinficant (NCS) or abnormal and clinically significant (CS) by the Investigator. There were no clinically relevant changes from baseline in mean clinical chemistry parameters over time and no clinically relevant differences in any laboratory parameter between any of the active treatment groups or the placebo group at any time point as assessed by the Investigator. Individual CS abnormalities were found for five patients, as reported in this end-point.
    End point type
    Secondary
    End point timeframe
    Clinical chemistry laboratory parameters were assessed at pre-specified visits from Visit 1 Screening to Visit 6 (Week 28). In addition, for one subject an extra visit in between week 14 and week 26 was scheduled for assessment of AST.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44 [104]
    45 [105]
    46 [106]
    Units: Number of subjects
        Abnormal CS finding - Week 26
    1
    1
    1
        Abnormal CS finding - Week 28
    1
    0
    0
        Abnormal CS finding - Extra Visit 1 subject only
    0
    1
    0
    Notes
    [104] - At Week 28, 44 subjects remained in the study. For each specific analysis n may however vary.
    [105] - At Week 28, 45 subjects remained in the study. For each specific analysis n may however vary.
    [106] - At Week 28, 46 subjects remained in the study. For each specific analysis n may however vary.
    No statistical analyses for this end point

    Secondary: Abnormal CS findings in hematology, coagulation and urinalysis

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    End point title
    		 Abnormal CS findings in hematology, coagulation and urinalysis
    End point description
    Blood samples for analysis of hematology and coagulation parameters were collected through venipuncture and analyzed by routine analytical methods. Urine analysis was performed at each research clinic using dip sticks. Parameter values were assessed as normal, abnormal but not clinically signinficant (NCS) or abnormal and clinically significant (CS) by the Investigator. There were no clinically relevant changes from baseline in mean hematology, coagulation or urinalysis parameters over time and no clinically relevant differences in any laboratory parameter between any of the active treatment groups or the placebo group at any time point as assessed by the Investigator. All hematology, coagulation and urinalysis values were assessed as normal or abnormal NCS. This end-point reports the number of abnormal CS findings for hematology, coagulation or urinalysis parameters (none).
    End point type
    Secondary
    End point timeframe
    Hematology, coagulation and urinalysis parameters were assessed at pre-specified visits from Visit 1 Screening to Visit 6 (Week 28).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    44 [107]
    45 [108]
    46 [109]
    Units: Number of abnormal CS findings
        Abnormal CS findings
    0
    0
    0
    Notes
    [107] - At Week 28, 44 subjects remained in the study. For each specific analysis n may however vary.
    [108] - At Week 28, 45 subjects remained in the study. For each specific analysis n may however vary.
    [109] - At Week 28, 46 subjects remained in the study. For each specific analysis n may however vary.
    No statistical analyses for this end point

    Secondary: Treatment compliance

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    End point title
    		 Treatment compliance
    End point description
    This end-point reports the IMP compliance (%), calculated as follows: compliance=(number of delivered capsules − number of returned capsules)/number of delivered capsules The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    Compliance was calculated for subjects who had completed the whole treatment period.
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    45
    46
    49
    Units: percent
        arithmetic mean (standard deviation)
    95 ± 10
    96 ± 5
    93 ± 10
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in GSRS total score

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    End point title
    		 Absolute change from baseline in GSRS total score
    End point description
    The gastrointestinal symptom rating scale (GSRS) questionnaire contains 15 items in 5 dimensions (diarrhea syndrome, indigestion syndrome, constipation syndrome, abdominal pain syndrome and reflux syndrome) and uses a 7-graded Likert scale where 1 represents the most positive option and 7 the most negative one (no discomfort at all, minor discomfort, mild discomfort, moderate discomfort, moderately severe discomfort, severe discomfort, very severe discomfort). This end-point reports the mean absolute change from baseline in GSRS total score at end of Week 2, end of Week 4, Week 7, End of Week 8, Week 14 and Week 26. The data presented for this end-point was based on the full analysis set (FAS), i.e. all subjects who were randomised and received at least one dose of the IMP and who had at least one post-baseline assessment of efficacy data.
    End point type
    Secondary
    End point timeframe
    The GSRS questionnaire was answered by the subjects at Visit 2 (Day 1, Baseline), end of Week 2 and 4, Visit 3 (Week 7), end of Week 8, Visit 4 (Week 14) and Visit 5 (Week 26).
    End point values
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Number of subjects analysed
    52 [110]
    49 [111]
    51 [112]
    Units: number
    arithmetic mean (standard deviation)
        End of Week 2
    0.6 ± 0.7
    0.7 ± 0.6
    0.3 ± 0.6
        End of Week 4
    0.7 ± 0.7
    0.7 ± 0.5
    0.3 ± 0.5
        Week 7
    0.9 ± 0.7
    0.9 ± 0.7
    0.3 ± 0.5
        End of Week 8
    0.8 ± 0.8
    0.9 ± 0.7
    0.4 ± 0.5
        Week 14
    0.8 ± 0.9
    1.0 ± 0.7
    0.3 ± 0.5
        Week 26
    0.6 ± 0.8
    0.7 ± 0.7
    0.1 ± 0.4
    Notes
    [110] - n=52 for Week 2 n=49 for Week 4 n=45 for Week 7 n=48 for Week 8 n=42 for Week 14 & 26
    [111] - n=49 for Week 2, 4 & 8 n=41 for Week 7 n=45 for Week 14 n=42 for Week 26
    [112] - n=51 for Week 2 n=52 for Week 4 n=45 for Week 7 n=49 for Week 8 n=48 for Week 14 n=47 for W 26
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - End of Week 2
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0271
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - End of Week 2
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate.
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0033
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - End of Week 4
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 101 (the number 103 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - End of Week 4
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 101 (the number 100 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0005
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 103 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 7
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 86 (the number 100 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - End of Week 8
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 97 (the number 103 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - End of Week 8
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 98 (the number 100 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0008
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 90 (the number 103 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0015
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 14
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 93 (the number 100 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 120/40 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 89 (the number 103 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 120/40 v Placebo
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0017
    Method
    		 ANCOVA
    Confidence interval
    Statistical analysis title
    		 EMP16-02 - 150/50 VS placebo - Week 26
    Statistical analysis description
    The absolute change from baseline in total score were analyzed using ANCOVA, with treatment as independent variable and body weight at baseline as covariate. The total number of subjects included in the analysis was 89 (the number 100 refers to End of Week 2).
    Comparison groups
    EMP16-02 - 150/50 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs (including serious AEs [SAEs]) were collected from the start of IMP administration until the end-of-study visit of each part.
    Adverse event reporting additional description
    The grading of the severity of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly or probably related to the IMP. GI symptoms were recorded using the GSRS questionnaire. Only symptoms assessed by the Investigator as severe were recorded as AEs unless the GI symptom led to an early withdrawal.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    EMP16-02 - 120/40
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02 -120/40 (120 mg orlistat/40 mg acarbose).

    Reporting group title
    EMP16-02 - 150/50
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive EMP16-02-150/50 (150 mg orlistat/50 mg acarbose).

    Reporting group title
    Placebo
    Reporting group description
    		 In this study patients were randomized in a 1:1:1 ratio to either of 2 doses of EMP16-02 or placebo. This arm (n=52) represents the group of patients who were randomized to receive placebo.

    Serious adverse events
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 EMP16-02 - 120/40 EMP16-02 - 150/50 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    32 / 52 (61.54%)
    39 / 52 (75.00%)
    30 / 52 (57.69%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Surgical and medical procedures
    Knee operation
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Skin neoplasm excision
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Toe operation
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Condition aggravated
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Fatigue
         subjects affected / exposed
    1 / 52 (1.92%)
    3 / 52 (5.77%)
    0 / 52 (0.00%)
         occurrences all number
    1
    3
    0
    Inflammation
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Sensation of foreign body
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Reproductive system and breast disorders
    Haematospermia
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Menometrorrhagia
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Ovarian cyst
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 52 (1.92%)
    2 / 52 (3.85%)
    0 / 52 (0.00%)
         occurrences all number
    1
    2
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    2 / 52 (3.85%)
         occurrences all number
    0
    0
    2
    Hallucination, auditory
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Major depression
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Road traffic accident
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    1
    Thermal burn
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    4 / 52 (7.69%)
    2 / 52 (3.85%)
    3 / 52 (5.77%)
         occurrences all number
    5
    2
    4
    Paresthesia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Ear and labyrinth disorders
    Otolithiasis
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Vertigo positional
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Retinal detachment
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal distension
         subjects affected / exposed
    4 / 52 (7.69%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    4
    1
    0
    Abdominal pain
         subjects affected / exposed
    2 / 52 (3.85%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    2
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Anal incontinence
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    defecation urgency
         subjects affected / exposed
    1 / 52 (1.92%)
    2 / 52 (3.85%)
    1 / 52 (1.92%)
         occurrences all number
    1
    2
    1
    Diarrhoea
         subjects affected / exposed
    8 / 52 (15.38%)
    8 / 52 (15.38%)
    0 / 52 (0.00%)
         occurrences all number
    9
    9
    0
    Dyspepsia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    1
    Encopresis
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    2
    0
    0
    Flatulence
         subjects affected / exposed
    4 / 52 (7.69%)
    3 / 52 (5.77%)
    1 / 52 (1.92%)
         occurrences all number
    4
    4
    1
    Food poisoning
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Gastrointestinal motility disorder
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroesophageal reflux disease
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    1
    Lip swelling
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Mucous stools
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Nausea
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Toothache
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Eczema
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Petechiae
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    1 / 52 (1.92%)
         occurrences all number
    0
    1
    1
    Rash
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Urticaria
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Renal and urinary disorders
    Hypertonic bladder
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 52 (0.00%)
    2 / 52 (3.85%)
    1 / 52 (1.92%)
         occurrences all number
    0
    3
    1
    Back pain
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    1
    0
    1
    Joint swelling
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Myositis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Neck pain
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Plantar fasciitis
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0
    Synovial cyst
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 52 (0.00%)
    6 / 52 (11.54%)
    2 / 52 (3.85%)
         occurrences all number
    0
    6
    2
    Ear infection
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    4 / 52 (7.69%)
    10 / 52 (19.23%)
    13 / 52 (25.00%)
         occurrences all number
    4
    10
    15
    Otitis media
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    2 / 52 (3.85%)
         occurrences all number
    0
    0
    2
    Urinary tract infection
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 52 (0.00%)
    1 / 52 (1.92%)
    1 / 52 (1.92%)
         occurrences all number
    0
    1
    1
    Food craving
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Gout
         subjects affected / exposed
    1 / 52 (1.92%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 52 (0.00%)
    0 / 52 (0.00%)
    1 / 52 (1.92%)
         occurrences all number
    0
    0
    1
    Increased appetite
         subjects affected / exposed
    1 / 52 (1.92%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences all number
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Nov 2020
    Addition of a voluntary, long-term follow-up visit 6 months after completion of the 26-weeks treatment period with EMP16 02 for assessment of weight, HbA1c and blood pressure. Addition of trough plasma concentration measurements of acarbose at steady state. Administrative changes, clarifications and corrections of typos.

    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.

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