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    Clinical Trial Results:
    A Phase 2b, Randomised, Parallel, Double-Blind Placebo-Controlled and Open-Label Active Comparator Study to Evaluate the Efficacy and Safety of Cotadutide in the Treatment of Overweight and Obese Subjects with Type 2 Diabetes Mellitus

    Summary
    EudraCT number
    		 2017-000626-35
    Trial protocol
    		 HU   CZ   SK   BG  
    Global end of trial date
    16 Jul 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Jun 2020
    First version publication date
    21 Jun 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D5670C00004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    151 85, Södertälje, Sweden,
    Public contact
    AstraZenenca Information Center, AstraZeneca, +1 18772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 18772409479, information.center@astrazeneca.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
    16 Jul 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Jul 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jul 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on HbA1c and body weight versus placebo
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/GCP, applicable regulatory requirements, and the AstraZeneca policy on Bioethics and Human Biological Smaples.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Aug 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 71
    Country: Number of subjects enrolled
    Canada: 56
    Country: Number of subjects enrolled
    Mexico: 61
    Country: Number of subjects enrolled
    Bulgaria: 78
    Country: Number of subjects enrolled
    Czech Republic: 63
    Country: Number of subjects enrolled
    Slovakia: 104
    Country: Number of subjects enrolled
    Germany: 148
    Country: Number of subjects enrolled
    Russian Federation: 253
    Worldwide total number of subjects
    834
    EEA total number of subjects
    393
    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)
    635
    From 65 to 84 years
    199
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Date first participant signed informed consent was 2 August 2017 and the date of last participant visit was 14 June 2019. This study was conducted at 20 sites in 8 countries.

    Pre-assignment
    Screening details
    		 A total of 1154 subjects consented to participate in the study; 834 participants were randomized and treated. Of the 320 participants not randomized to a treatment group: 307 No longer met study criteria, 9 withdrew consent, 1 was non-compliant with study drug, and 3 did not continue for other reasons.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    once daily IV administration

    Arm title
    		 Liraglutide
    Arm description
    		 Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Liraglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    6.0 mg/mL once daily SC administration

    Arm title
    		 MEDI0382 100 mcg
    Arm description
    		 MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI0382
    Investigational medicinal product code
    Other name
    Cotadutide
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mcg once daily IV administration

    Arm title
    		 MEDI0382 200 mcg
    Arm description
    		 MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI0382
    Investigational medicinal product code
    Other name
    Cotadutide
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    200 mcg once daily IV administration

    Arm title
    		 MEDI0382 300 mcg
    Arm description
    		 MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
    Arm type
    		 Experimental

    Investigational medicinal product name
    MEDI0382
    Investigational medicinal product code
    Other name
    Cotadutide
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    300 mcg once daily IV administration

    Number of subjects in period 1
    		Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Started
    112
    110
    100
    256
    256
    Completed
    108
    105
    96
    242
    245
    Not completed
    4
    5
    4
    14
    11
         Adverse event, serious fatal
    -
    -
    -
    2
    1
         Consent withdrawn by subject
    3
    2
    2
    5
    7
         Adverse event, non-fatal
    -
    -
    1
    4
    1
         Other reasons
    -
    1
    -
    1
    2
         Lost to follow-up
    1
    2
    1
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    Liraglutide
    Reporting group description
    		 Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    MEDI0382 100 mcg
    Reporting group description
    		 MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    MEDI0382 200 mcg
    Reporting group description
    		 MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    MEDI0382 300 mcg
    Reporting group description
    		 MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group values
    		 Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg Total
    Number of subjects
    		 112 110 100 256 256 834
    Age categorical
    Units: Subjects
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 84 88 78 195 190 635
        From 65-84 years
    		 28 22 22 61 66 199
        85 years and over
    		 0 0 0 0 0 0
        In Utero
    		 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 57.3 ± 9.5 55.5 ± 9.8 57.6 ± 9.9 57.3 ± 9.9 56.3 ± 10.2 -
    Sex: Female, Male
    Units:
        Female
    		 55 60 57 147 129 448
        Male
    		 57 50 43 109 127 386
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 3 3 0 5 0 11
        Asian
    		 1 1 0 3 1 6
        Black or African American
    		 0 3 1 3 3 10
        White
    		 107 103 99 245 252 806
        Other
    		 1 0 0 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    Liraglutide
    Reporting group description
    		 Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    MEDI0382 100 mcg
    Reporting group description
    		 MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    MEDI0382 200 mcg
    Reporting group description
    		 MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Reporting group title
    MEDI0382 300 mcg
    Reporting group description
    		 MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

    Primary: Change in HbA1c at Week 14

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    End point title
    		 Change in HbA1c at Week 14 [1]
    End point description
    To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
    End point type
    Primary
    End point timeframe
    From baseline to 14 weeks
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this primary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on HbA1c and body weight versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: percentage
        least squares mean (confidence interval 95%)
    -0.18 (-0.34 to -0.02)
    -1.01 (-1.18 to -0.84)
    -1.22 (-1.33 to -1.11)
    -1.09 (-1.20 to -0.98)
    Statistical analysis title
    		 Primary Endpoint Analysis
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.06
         upper limit
    		 -0.59
    Statistical analysis title
    		 Primary Endpoint Analysis
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.23
         upper limit
    		 -0.85
    Statistical analysis title
    		 Primary Endpoint Analysis
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.11
         upper limit
    		 -0.72

    Primary: Percent change in body weight at Week 14

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    End point title
    		 Percent change in body weight at Week 14 [2]
    End point description
    To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo
    End point type
    Primary
    End point timeframe
    From baseline to 14 weeks
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this primary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on HbA1c and body weight versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: percentage
        least squares mean (confidence interval 95%)
    -0.70 (-1.44 to 0.04)
    -2.70 (-3.49 to -1.91)
    -3.47 (-3.95 to -2.98)
    -4.33 (-4.82 to -3.84)
    Statistical analysis title
    		 Primary Endpoint Analysis
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.08
         upper limit
    		 -0.91
    Statistical analysis title
    		 Primary Endpoint Analysis
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.65
         upper limit
    		 -1.87
    Statistical analysis title
    		 Primary Endpoint Analysis
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.51
         upper limit
    		 -2.73

    Secondary: Change in HbA1c at Weeks 26 and 54

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    End point title
    		 Change in HbA1c at Weeks 26 and 54 [3]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on HbA1c versus placebo
    End point type
    Secondary
    End point timeframe
    from baseline to 26 weeks and 54 weeks
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on additional measures of glycaemic control and body weight versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: percentage
    least squares mean (confidence interval 95%)
        from baseline to 26 weeks
    -0.40 (-0.58 to -0.22)
    -1.06 (-1.25 to -0.87)
    -1.22 (-1.34 to -1.10)
    -1.12 (-1.24 to -1.00)
        from baseline to 54 weeks
    -0.44 (-0.63 to -0.24)
    -0.96 (-1.16 to -0.75)
    -1.06 (-1.19 to -0.93)
    -1.01 (-1.14 to -0.88)
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.92
         upper limit
    		 -0.4
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.03
         upper limit
    		 -0.6
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.94
         upper limit
    		 -0.51
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 -0.24
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.86
         upper limit
    		 -0.39
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 -0.34

    Secondary: Percentage of participants achieving an HbA1c target < 7.0%

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    End point title
    		 Percentage of participants achieving an HbA1c target < 7.0% [4]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of participants achieving an HbA1c target of <7% versus placebo
    End point type
    Secondary
    End point timeframe
    after 14, 26, and 54 weeks
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on additional measures of glycaemic control and body weight versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: participants
        after 14 weeks
    19
    50
    143
    143
        after 26 weeks
    25
    48
    139
    143
        after 54 weeks
    23
    52
    125
    128
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 14
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    6.67
    Confidence interval
         level
    		 92%
         sides
    2-sided
         lower limit
    		 3.34
         upper limit
    		 13.3
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 14
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    9.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.39
         upper limit
    		 18.36
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 14
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    8.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.65
         upper limit
    		 15.61
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    3.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.98
         upper limit
    		 7.03
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    5.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.13
         upper limit
    		 9.34
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.02
         upper limit
    		 8.97
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    4.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.61
         upper limit
    		 9.36
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    4.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.62
         upper limit
    		 7.89
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    4.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.51
         upper limit
    		 7.51

    Secondary: Percent change in body weight at Weeks 26 and 54

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    End point title
    		 Percent change in body weight at Weeks 26 and 54 [5]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo
    End point type
    Secondary
    End point timeframe
    from baseline to 26 weeks and 54 weeks
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on additional measures of glycaemic control and body weight versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: percentage
    least squares mean (confidence interval 95%)
        from baseline to 26 weeks
    -1.14 (-1.99 to -0.29)
    -3.23 (-4.13 to -2.32)
    -3.94 (-4.51 to -3.38)
    -4.60 (-5.17 to -4.04)
        from baseline to 54 weeks
    -0.84 (-1.82 to 0.14)
    -3.27 (-4.32 to -2.22)
    -3.08 (-3.73 to -2.43)
    -4.16 (-4.81 to -3.50)
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.32
         upper limit
    		 -0.85
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.82
         upper limit
    		 -1.79
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.48
         upper limit
    		 -2.44
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.86
         upper limit
    		 -1
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.41
         upper limit
    		 -1.06
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.49
         upper limit
    		 -2.14

    Secondary: Absolute change in body weight

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    End point title
    		 Absolute change in body weight [6]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo
    End point type
    Secondary
    End point timeframe
    from baseline to 14 weeks, 26 weeks and 54 weeks
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on additional measures of glycaemic control and body weight versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: kg
    least squares mean (confidence interval 95%)
        from baseline to 14 weeks
    -0.71 (-1.44 to 0.03)
    -2.66 (-3.45 to -1.87)
    -3.45 (-3.94 to -2.97)
    -4.42 (-4.91 to -3.93)
        from baseline to 26 weeks
    -1.20 (-2.06 to -0.34)
    -3.20 (-4.13 to -2.28)
    -3.94 (-4.52 to -3.37)
    -4.75 (-5.33 to -4.18)
        from baseline to 54 weeks
    -0.94 (-1.94 to 0.07)
    -3.20 (-4.28 to -2.12)
    -3.09 (-3.77 to -2.42)
    -4.35 (-5.03 to -3.68)
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 14
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.03
         upper limit
    		 -0.87
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 14
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.63
         upper limit
    		 -1.86
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 14
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 -2.82
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.002
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.27
         upper limit
    		 -0.74
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.78
         upper limit
    		 -1.71
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 26
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.59
         upper limit
    		 -2.52
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.003
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.74
         upper limit
    		 -0.79
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.37
         upper limit
    		 -0.95
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Week 54
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.63
         upper limit
    		 -2.2

    Secondary: Percent change in body weight versus active comparator

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    End point title
    		 Percent change in body weight versus active comparator [7]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily
    End point type
    Secondary
    End point timeframe
    from baseline to 14 weeks, 26 weeks and 54 weeks
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on weight versus liraglutide 1.8 mg once daily.
    End point values
    		 Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    110
    100
    256
    256
    Units: percentage
    least squares mean (confidence interval 95%)
        Percent change at 14 weeks
    -3.40 (-4.14 to -2.65)
    -2.70 (-3.49 to -1.91)
    -3.47 (-3.95 to -2.98)
    -4.33 (-4.82 to -3.84)
        Percent change at 26 weeks
    -4.12 (-4.98 to -3.27)
    -3.23 (-4.13 to -2.32)
    -3.94 (-4.51 to -3.38)
    -4.60 (-5.17 to -4.04)
        Percent change at 54 weeks
    -3.20 (-4.19 to -2.21)
    -3.27 (-4.32 to -2.22)
    -3.08 (-3.73 to -2.43)
    -4.16 (-4.81 to -3.50)
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 14
    Comparison groups
    Liraglutide v MEDI0382 100 mcg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.211
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.39
         upper limit
    		 1.79
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 14
    Comparison groups
    Liraglutide v MEDI0382 200 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.881
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.96
         upper limit
    		 0.83
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 14
    Comparison groups
    Liraglutide v MEDI0382 300 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.042
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.82
         upper limit
    		 -0.04
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 26
    Comparison groups
    Liraglutide v MEDI0382 100 mcg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.158
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.35
         upper limit
    		 2.14
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 26
    Comparison groups
    Liraglutide v MEDI0382 200 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.734
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.85
         upper limit
    		 1.2
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 26
    Comparison groups
    Liraglutide v MEDI0382 300 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.357
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.51
         upper limit
    		 0.54
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 54
    Comparison groups
    Liraglutide v MEDI0382 100 mcg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.921
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.51
         upper limit
    		 1.37
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 54
    Comparison groups
    Liraglutide v MEDI0382 200 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.847
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.07
         upper limit
    		 1.3
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Percent change at Week 54
    Comparison groups
    Liraglutide v MEDI0382 300 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.112
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.15
         upper limit
    		 0.22

    Secondary: Absolute change in body weight versus active comparator

    		 Close Top of page
    End point title
    		 Absolute change in body weight versus active comparator [8]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily
    End point type
    Secondary
    End point timeframe
    from baseline to 14 weeks, 26 weeks and 54 weeks
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on weight versus liraglutide 1.8 mg once daily.
    End point values
    		 Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    110
    100
    256
    256
    Units: kg
    least squares mean (confidence interval 95%)
        Absolute change at 14 weeks
    -3.25 (-4.00 to -2.51)
    -2.66 (-3.45 to -1.87)
    -3.45 (-3.94 to -2.97)
    -4.42 (-4.91 to -3.93)
        Absolute change at 26 weeks
    -3.90 (-4.77 to -3.03)
    -3.20 (-4.13 to -2.28)
    -3.94 (-4.52 to -3.37)
    -4.75 (-5.33 to -4.18)
        Absolute change at 54 weeks
    -2.94 (-3.96 to -1.92)
    -3.20 (-4.28 to -2.12)
    -3.09 (-3.77 to -2.42)
    -4.35 (-5.03 to -3.68)
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 14
    Comparison groups
    Liraglutide v MEDI0382 100 mcg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.284
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.49
         upper limit
    		 1.68
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 14
    Comparison groups
    Liraglutide v MEDI0382 200 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.658
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.09
         upper limit
    		 0.69
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 14
    Comparison groups
    Liraglutide v MEDI0382 300 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.01
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.06
         upper limit
    		 -0.27
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 26
    Comparison groups
    Liraglutide v MEDI0382 100 mcg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.279
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.57
         upper limit
    		 1.97
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 26
    Comparison groups
    Liraglutide v MEDI0382 200 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.94
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.08
         upper limit
    		 1
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 26
    Comparison groups
    Liraglutide v MEDI0382 300 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.11
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.89
         upper limit
    		 0.19
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 54
    Comparison groups
    Liraglutide v MEDI0382 100 mcg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.73
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.74
         upper limit
    		 1.22
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 54
    Comparison groups
    Liraglutide v MEDI0382 200 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.804
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.38
         upper limit
    		 1.07
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    Absolute change at Week 54
    Comparison groups
    Liraglutide v MEDI0382 300 mcg
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.023
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.63
         upper limit
    		 -0.19

    Secondary: Percentage of participants achieving weight loss of ≥5% and ≥10%

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    End point title
    		 Percentage of participants achieving weight loss of ≥5% and ≥10% [9]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of subjects achieving weight loss of ≥5% and ≥10% versus placebo
    End point type
    Secondary
    End point timeframe
    after 14 weeks, 26 weeks and 54 weeks
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on additional measures of glycaemic control and body weight versus placebo
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: participants
        Participants with weight loss ≥5% at Wk 14 (LOCF)
    3
    18
    65
    92
        Participants with weight loss ≥5% at Wk 26 (LOCF)
    11
    28
    76
    110
        Participants with weight loss ≥5% at Wk 54 (LOCF)
    14
    34
    71
    98
        Participants with weight loss ≥10% at Wk 14 (LOCF)
    0
    6
    15
    20
        Participants with weight loss ≥10% at Wk 26 (LOCF)
    1
    7
    28
    27
        Participants with weight loss ≥10% at Wk 54 (LOCF)
    2
    11
    21
    32
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 14
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    8.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.38
         upper limit
    		 29.43
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 14
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    12.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.82
         upper limit
    		 40.64
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 14
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    21.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.55
         upper limit
    		 68.97
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 26
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    3.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.72
         upper limit
    		 7.89
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 26
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    3.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2
         upper limit
    		 7.78
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 26
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    7.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.72
         upper limit
    		 14.24
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 54
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    3.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.84
         upper limit
    		 7.45
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 54
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.002
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    2.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.46
         upper limit
    		 5.09
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=5% at Week 54
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Log odds ratio
    Point estimate
    4.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.42
         upper limit
    		 8.3
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=10% at Week 26
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.048
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    8.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 70.17
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=10% at Week 26
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.01
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    13.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.85
         upper limit
    		 102.91
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=10% at Week 26
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.012
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    13.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.75
         upper limit
    		 97.68
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=10% at Week 54
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.013
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    6.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.49
         upper limit
    		 32.07
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=10% at Week 54
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.032
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    4.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.15
         upper limit
    		 21.6
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    weight loss >=10% at Week 54
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.005
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    7.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.86
         upper limit
    		 33.64

    Secondary: Proportion of subjects rescued or discontinued for lack of glycaemic control

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    End point title
    		 Proportion of subjects rescued or discontinued for lack of glycaemic control [10]
    End point description
    To assess the effect of 100, 200, and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo
    End point type
    Secondary
    End point timeframe
    at 14 weeks, 26 weeks and 54 weeks
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to assess the effect of 100 μg, 200 μg and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: participants
        received rescue medication at 14 wks
    11
    1
    3
    2
        received rescue medication at 26 wks
    20
    3
    8
    6
        received rescue medication at 54 wks
    34
    10
    26
    24
        discontinued study IP at 14 wks
    2
    0
    1
    0
        discontinued study IP at 26 wks
    4
    1
    2
    0
        discontinued study IP at 54 wks
    4
    1
    3
    0
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 14 wks
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.024
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.73
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 14 wks
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 0.4
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 14 wks
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 0.33
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 26 wks
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.002
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 0.48
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 26 wks
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 0.34
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 26 wks
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 0.28
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 54 wks
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.11
         upper limit
    		 0.53
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 54 wks
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 0.44
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    received rescue medication at 54 wks
    Comparison groups
    Placebo v MEDI0382 300 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.12
         upper limit
    		 0.41
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    discontinued IP at 14 wks
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.216
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 2.43
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    discontinued IP at 26 wks
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.253
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 2.52
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    discontinued IP at 26 wks
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.079
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 1.19
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    discontinued IP at 54 wks
    Comparison groups
    Placebo v MEDI0382 100 mcg
    Number of subjects included in analysis
    212
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.252
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 2.5
    Statistical analysis title
    		 Secondary Endpoint Analysis
    Statistical analysis description
    discontinued IP at 54 wks
    Comparison groups
    Placebo v MEDI0382 200 mcg
    Number of subjects included in analysis
    368
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.143
    Method
    		 Regression, Logistic
    Parameter type
    		 Log odds ratio
    Point estimate
    0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.07
         upper limit
    		 1.47

    Secondary: Pharmacokinetic (PK) endpoint: Trough plasma concentration (Cmin)

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    End point title
    		 Pharmacokinetic (PK) endpoint: Trough plasma concentration (Cmin) [11]
    End point description
    To characterise the PK profile of 100, 200, and 300 μg of cotadutide
    End point type
    Secondary
    End point timeframe
    during dosing and follow-up (minimum 54 weeks)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to characterise the PK profile and immunogenicity of 100 μg, 200 μg and 300 μg of cotadutide.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    0 [12]
    100
    256
    256
    Units: ng/mL
    arithmetic mean (standard deviation)
        Week 1
    ±
    2.68 ± 1.27
    2.76 ± 1.88
    2.77 ± 1.84
        Week 2
    ±
    2.66 ± 1.61
    5.13 ± 3.23
    5.18 ± 3.05
        Week 6
    ±
    2.75 ± 1.44
    5.20 ± 3.57
    7.77 ± 4.88
        Week 10
    ±
    3.18 ± 2.26
    5.74 ± 4.23
    8.23 ± 4.31
        Week 14
    ±
    3.79 ± 4.05
    6.50 ± 5.26
    9.71 ± 7.64
        Week 18
    ±
    4.58 ± 5.04
    7.43 ± 6.43
    10.8 ± 7.95
        Week 22
    ±
    4.63 ± 4.28
    8.07 ± 7.01
    11.5 ± 9.77
        Week 26
    ±
    4.39 ± 3.33
    8.12 ± 7.31
    12.9 ± 12.1
        Week 54
    ±
    4.58 ± 3.89
    8.99 ± 9.22
    13.2 ± 14.3
    Notes
    [12] - study objective was to characterise the trough plasma concentration of 100, 200, 300 μg MEDI0382
    No statistical analyses for this end point

    Secondary: Immunogenicity endpoint: Overall ADA incidence (if positive)

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    End point title
    		 Immunogenicity endpoint: Overall ADA incidence (if positive) [13]
    End point description
    To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide
    End point type
    Secondary
    End point timeframe
    during dosing and follow-up (minimum 54 weeks)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to characterise the PK profile and immunogenicity of 100 μg, 200 μg and 300 μg of cotadutide.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: participants
        ADA positive at baseline
    1
    1
    0
    0
        ADA incidence
    3
    55
    152
    155
        ADA positive post-baseline
    3
    54
    152
    155
    No statistical analyses for this end point

    Secondary: Immunogenicity endpoint: ADA response to MEDI0382 (if positive)

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    End point title
    		 Immunogenicity endpoint: ADA response to MEDI0382 (if positive) [14]
    End point description
    To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide
    End point type
    Secondary
    End point timeframe
    during dosing and follow-up (minimum 54 weeks)
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis for this secondary study objective is to characterise the PK profile and immunogenicity of 100 μg, 200 μg and 300 μg of cotadutide.
    End point values
    		 Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Number of subjects analysed
    112
    100
    256
    256
    Units: titer
    median (full range (min-max))
        ADA positive at baseline, median titer
    5.0 (5 to 5)
    5.0 (5 to 5)
    0 (0 to 0)
    0 (0 to 0)
        ADA incidence, median of maximum titer
    5.0 (5 to 20)
    20.0 (5 to 2560)
    20.0 (5 to 640)
    20.0 (5 to 5120)
        ADA positive post-baseline, median of max. titer
    5.0 (5 to 20)
    20.0 (5 to 2560)
    20.0 (5 to 640)
    20.0 (5 to 5120)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until last study visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    		 -

    Reporting group title
    MEDI0382 100 mcg
    Reporting group description
    		 -

    Reporting group title
    MEDI0382 200 mcg
    Reporting group description
    		 -

    Reporting group title
    MEDI0382 300 mcg
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Liraglutide 1.8 mg MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 112 (10.71%)
    8 / 110 (7.27%)
    12 / 100 (12.00%)
    33 / 256 (12.89%)
    20 / 256 (7.81%)
         number of deaths (all causes)
    0
    0
    0
    2
    1
         number of deaths resulting from adverse events
    0
    0
    0
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Triple negative breast cancer
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    2 / 256 (0.78%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Impaired healing
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Acquired phimosis
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphonia
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Vocal cord dysfunction
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic leak
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial bypass occlusion
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural fistula
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    2 / 256 (0.78%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    2 / 256 (0.78%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Silent myocardial infarction
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    2 / 256 (0.78%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal tear
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Megacolon
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    2 / 256 (0.78%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder polyp
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perinephritis
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract disorder
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthrofibrosis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma muscle
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscal degeneration
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    3 / 256 (1.17%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Acarodermatitis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    1 / 100 (1.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    2 / 100 (2.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    1 / 256 (0.39%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    1 / 256 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 112 (0.00%)
    1 / 110 (0.91%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 112 (0.89%)
    0 / 110 (0.00%)
    0 / 100 (0.00%)
    0 / 256 (0.00%)
    0 / 256 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Liraglutide 1.8 mg MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    68 / 112 (60.71%)
    67 / 110 (60.91%)
    72 / 100 (72.00%)
    198 / 256 (77.34%)
    203 / 256 (79.30%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 112 (2.68%)
    0 / 110 (0.00%)
    4 / 100 (4.00%)
    11 / 256 (4.30%)
    15 / 256 (5.86%)
         occurrences all number
    3
    0
    5
    12
    19
    Headache
         subjects affected / exposed
    1 / 112 (0.89%)
    5 / 110 (4.55%)
    3 / 100 (3.00%)
    15 / 256 (5.86%)
    19 / 256 (7.42%)
         occurrences all number
    1
    5
    4
    18
    23
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    2 / 112 (1.79%)
    2 / 110 (1.82%)
    1 / 100 (1.00%)
    10 / 256 (3.91%)
    13 / 256 (5.08%)
         occurrences all number
    2
    3
    1
    10
    14
    Diarrhoea
         subjects affected / exposed
    10 / 112 (8.93%)
    4 / 110 (3.64%)
    13 / 100 (13.00%)
    49 / 256 (19.14%)
    28 / 256 (10.94%)
         occurrences all number
    10
    7
    15
    68
    40
    Dyspepsia
         subjects affected / exposed
    2 / 112 (1.79%)
    3 / 110 (2.73%)
    7 / 100 (7.00%)
    19 / 256 (7.42%)
    28 / 256 (10.94%)
         occurrences all number
    2
    3
    13
    26
    38
    Eructation
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 110 (0.00%)
    2 / 100 (2.00%)
    14 / 256 (5.47%)
    12 / 256 (4.69%)
         occurrences all number
    0
    0
    2
    17
    15
    Nausea
         subjects affected / exposed
    12 / 112 (10.71%)
    17 / 110 (15.45%)
    23 / 100 (23.00%)
    85 / 256 (33.20%)
    105 / 256 (41.02%)
         occurrences all number
    13
    21
    28
    115
    143
    Vomiting
         subjects affected / exposed
    5 / 112 (4.46%)
    3 / 110 (2.73%)
    10 / 100 (10.00%)
    51 / 256 (19.92%)
    43 / 256 (16.80%)
         occurrences all number
    6
    3
    12
    66
    58
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 112 (5.36%)
    2 / 110 (1.82%)
    8 / 100 (8.00%)
    9 / 256 (3.52%)
    9 / 256 (3.52%)
         occurrences all number
    6
    2
    8
    12
    9
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    15 / 112 (13.39%)
    11 / 110 (10.00%)
    11 / 100 (11.00%)
    22 / 256 (8.59%)
    28 / 256 (10.94%)
         occurrences all number
    19
    13
    13
    28
    44
    Respiratory tract infection viral
         subjects affected / exposed
    3 / 112 (2.68%)
    1 / 110 (0.91%)
    1 / 100 (1.00%)
    13 / 256 (5.08%)
    7 / 256 (2.73%)
         occurrences all number
    3
    1
    1
    15
    8
    Urinary tract infection
         subjects affected / exposed
    6 / 112 (5.36%)
    2 / 110 (1.82%)
    3 / 100 (3.00%)
    13 / 256 (5.08%)
    7 / 256 (2.73%)
         occurrences all number
    6
    2
    4
    17
    9
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 112 (0.89%)
    1 / 110 (0.91%)
    3 / 100 (3.00%)
    12 / 256 (4.69%)
    14 / 256 (5.47%)
         occurrences all number
    1
    1
    3
    12
    14

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Oct 2017
    Modified inclusion criteria to remove the upper BMI limit for the study. MET monotherapy, inclusion criterion 5, was modified to allow use of another glucose-lowering medication for up to 2 weeks in the 2 months prior to screening. Exclusion criterion 5 was modified to allow daily SC insulin treatment for up to 2 weeks within 90 days prior to screening. Exclusion criterion 13 was updated to present basal calcitonin values in pg/mL. Exclusion criterion 18 was clarified to restrict enrolment of subjects with any history of psychosis or bipolar disorder; subjects with a history of major depressive disorder within the past year with the subject being clinically unstable. The protocol was modified to include collection of subjects’ vital status at the end of study. Updated schedule of screening procedures to refer to a 2-week period. Restrictions for tobacco and caffeine use for 24 hours prior to the visit were removed and additional options for retesting laboratory results were added. Updated schedule of procedures to include immunogenicity laboratory sampling at Visits 4 & 6. Modified the schedule of procedures for the 92-week extension period to remove the requirement of AE collection, concomitant medication review, vital signs collection, and brief PE during the IP resupply visits. Clarification on urine collection for urinalysis was added. Term pancreatitis as 1 of the adjudicated events was updated to pancreatic disease. Updated protocol to allow for MET withhold during persistent symptoms of nausea and vomiting. Updated permitted concomitant medications for consistency with inclusion criterion 5. Additional clarifications added on use of antiemetic therapy. 5HT-3 antagonist treatment recommendation removed from the text. Clarified PK population to refer to cotadutide-treated subjects only. A clarification was added to the protocol synopsis on the use of liraglutide in patients with CHF NYHA class III and label updates with the data from the LEADER trial.
    05 Feb 2018
    Protocol modified to exclude the interim analysis and the analysis associated with the 26-week data. Due to fast enrolment to the study, timing for the primary analysis advanced, so there was no longer a need for the interim analysis. Similarly, the separate analysis associated with the 26-week data was removed because fast enrolment lead to an insufficient number of subjects reaching 26 weeks at the time of the primary analysis to provide satisfactory statistical power.
    20 Apr 2018
    The methods for unblinding and statistical considerations were modified to include an analysis when all subject reached 26 weeks of treatment. To inform about efficacy at 6 months and guide the selection process for the optimal dose regimen because the impact of weight loss on improved insulin sensitivity and glucose control might not be adequately captured at 14 weeks. Information was added to include collection of specific information for events of pancreatic carcinoma. Description of clinical event adjudication updated to add pancreatic carcinoma and thyroid neoplasm to the list of adjudicated events. Given the controversy of whether GLP-1–based therapy increases the risk for specific malignant disease like pancreatic carcinoma and thyroid cancer, AstraZeneca decided to adjudicate pancreatic carcinoma and thyroid cancer in the Phase 2b study.
    04 Dec 2018
    Protocol updated to reduce the length of the treatment extension period from 92 to 40 weeks. The rationale for this change is to allow participants adequate time to transition to other therapies and allow continued collection of safety and efficacy data to inform further decisions regarding cotadutide doses.

    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
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