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    Clinical Trial Results:
    A randomised, double-blind, double-dummy, placebo-controlled, parallel-group multi-centre clinical proof-of-principle trial in adult subjects with newly diagnosed type 1 diabetes mellitus investigating the effect of NNC0114-0006 and liraglutide on preservation of beta-cell function.

    Summary
    EudraCT number
    		 2014-001215-39
    Trial protocol
    		 AT   PT   DK   FI   ES   IE   PL   BE  
    Global end of trial date
    27 Feb 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Feb 2020
    First version publication date
    28 Feb 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NN9828-4150
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02443155
    WHO universal trial number (UTN)
    		 U1111-1154-7172
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Allé, Bagsvaerd, Denmark, 2880
    Public contact
    Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, 2880 (+1) 866-867-7178, clinicaltrials@novonordisk.com
    Scientific contact
    Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, 2880 (+1) 866-867-7178, clinicaltrials@novonordisk.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
    17 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Aug 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Feb 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to evaluate the effect of NNC0114-0006, liraglutide and the combination of NNC0114 0006 and liraglutide, compared to placebo, on preservation of beta-cell function after 54 weeks of treatment in adult subjects with newly diagnosed type 1 diabetes mellitus (T1DM).
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice, including archiving of essential documents and FDA 21 CFR 312.120.
    Background therapy
    		 Not applicable.
    Evidence for comparator
    		 Not applicable.
    Actual start date of recruitment
    10 Nov 2015
    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
    Austria: 17
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Canada: 21
    Country: Number of subjects enrolled
    Denmark: 15
    Country: Number of subjects enrolled
    Finland: 4
    Country: Number of subjects enrolled
    Ireland: 6
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    Italy: 16
    Country: Number of subjects enrolled
    Norway: 1
    Country: Number of subjects enrolled
    Poland: 15
    Country: Number of subjects enrolled
    Portugal: 10
    Country: Number of subjects enrolled
    Russian Federation: 80
    Country: Number of subjects enrolled
    Spain: 29
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    Ukraine: 25
    Country: Number of subjects enrolled
    United Kingdom: 32
    Country: Number of subjects enrolled
    United States: 13
    Worldwide total number of subjects
    308
    EEA total number of subjects
    155
    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)
    308
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 94 sites in 17 countries screened subjects. Number of sites randomised subjects were Austria:4, Belgium:1, Canada:10, Denmark:2, Finland:2 of 3 sites, Ireland:3, Israel:4, Italy:4, Norway:1 of 2 sites, Poland:4, Portugal:3 of 4 sites, Russian Fed:13 of 15 sites, Spain:6 of 7 sites, Sweden:1 of 2 sites, Ukraine:6, UK:12, US:6 of 11 screened sites.

    Pre-assignment
    Screening details
    		 Not applicable.

    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
    Blinding implementation details
    The trial was double-blinded and the investigator and subjects remained blinded throughout the trial. The sponsor was blinded for the treatment period, but unblinded for the observation period.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 NNC0114-0006 + Liraglutide
    Arm description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NNC0114-0006 C 100 mg/ml
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received NNC0114-0006 dose of 12 mg/kg every 6 weeks, intravenously, at trial site.

    Investigational medicinal product name
    Liraglutide, 6.0 mg/mL,
    Investigational medicinal product code
    Other name
    Victoza
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    All subjects initiated 0.6 mg liraglutide, on the day of randomisation and the dose was escalated in increments of 0.6 mg liraglutide every 2 weeks until the target dose of 1.8 mg liraglutide was reached. Liraglutide was self-administered once daily, subcutaneously, either in the abdomen, thigh or upper arm daily with a pen-injector around the same time of the day.

    Arm title
    		 NNC0114-0006
    Arm description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took liraglutide placebo once daily, subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NNC0114-0006 C 100 mg/ml
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received NNC0114-0006 dose of 12 mg/kg every 6 weeks, intravenously, at trial site.

    Investigational medicinal product name
    Liraglutide placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects took liraglutide placebo once daily subcutaneously, with the volume of placebo equivalent to the volume Liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Liraglutide placebo was self-administered either in the abdomen, thigh or upper arm daily with a pen-injector around the same time of the day.

    Arm title
    		 Liraglutide
    Arm description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Liraglutide
    Investigational medicinal product code
    Other name
    Victoza
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    All subjects initiated 0.6 mg liraglutide, on the day of randomisation and the dose was escalated in increments of 0.6 mg liraglutide every 2 weeks until the target dose of 1.8 mg liraglutide was reached. Liraglutide was self-administered once daily, subcutaneously, either in the abdomen, thigh or upper arm daily with a pen-injector around the same time of the day.

    Investigational medicinal product name
    NNC0114-0006 placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously, at trial site.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. In addition to that, subjects took liraglutide placebo once daily subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.
    Arm type
    		 Placebo

    Investigational medicinal product name
    NNC0114-0006 placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously, at trial site.

    Investigational medicinal product name
    Liraglutide placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects took liraglutide placebo once daily subcutaneously, with the volume of placebo equivalent to the volume Liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Liraglutide placebo was self-administered either in the abdomen, thigh or upper arm daily with a pen-injector around the same time of the day.

    Number of subjects in period 1 [1]
    		NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Started
    77
    77
    76
    77
    Completed
    65
    63
    67
    61
    Not completed
    12
    14
    9
    16
         Adverse event, serious fatal
    -
    -
    1
    -
         Consent withdrawn by subject
    4
    7
    3
    9
         Adverse event, non-fatal
    3
    4
    1
    2
         Pregnancy
    3
    1
    1
    2
         Unclassified
    -
    -
    2
    1
         Lost to follow-up
    1
    2
    -
    1
         Protocol deviation
    1
    -
    1
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: One (1) subject was randomised to liraglutide but was withdrawn from the trial before exposure to trial products. Hence the number of subjects 'started' in Liraglutide arm is 76 and not 77.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    NNC0114-0006 + Liraglutide
    Reporting group description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    NNC0114-0006
    Reporting group description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took liraglutide placebo once daily, subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    Liraglutide
    Reporting group description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. In addition to that, subjects took liraglutide placebo once daily subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo Total
    Number of subjects
    		 77 77 76 77 307
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 77 77 76 77 307
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 28.0 ± 7.5 28.6 ± 7.9 28.0 ± 7.1 29.0 ± 7.0 -
    Gender Categorical
    Units: Subjects
        Female
    		 21 32 25 28 106
        Male
    		 56 45 51 49 201

    End points

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    End points reporting groups
    Reporting group title
    NNC0114-0006 + Liraglutide
    Reporting group description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    NNC0114-0006
    Reporting group description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took liraglutide placebo once daily, subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    Liraglutide
    Reporting group description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. In addition to that, subjects took liraglutide placebo once daily subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Primary: AUC0-4h, C-peptide, 54w/AUC0-4h, C-peptide, baseline: AUC0-4h for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve.

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    End point title
    		 AUC0-4h, C-peptide, 54w/AUC0-4h, C-peptide, baseline: AUC0-4h for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve.
    End point description
    Area under the curve, from 0 to 4 hours (AUC0-4h) for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve at week 54 was measured as ratio to baseline value. C-peptide concentration was measured in unit 'nmol*h/L'.
    End point type
    Primary
    End point timeframe
    At week 54 relative to baseline (defined as the MMTT performed at Visit 2)
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    66
    65
    68
    63
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.934 ± 61.9
    0.783 ± 45.5
    0.709 ± 104.8
    0.660 ± 86.3
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    NNC0114-0006+Liraglutide/Placebo. Ratio of week 54 to baseline are analysed using mixed model for repeated measurements (MMRM) with an unstructured covariance matrix. Treatment, stratum and sex as factors and log baseline value and age as covariates, including the interaction between visit and all variables.
    Comparison groups
    Placebo v NNC0114-0006 + Liraglutide
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.0017
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.16
         upper limit
    		 1.89
    Notes
    [1] - Due to the repeated analysis, the number of subjects included in the analysis were 148 and not only the 129 with an endpoint value at week 54.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    NNC0114-0006 /Placebo. Ratio of week 54 to baseline are analysed using MMRM with an unstructured covariance matrix. Treatment, stratum and sex as factors and log baseline value and age as covariates, including the interaction between visit and all variables.
    Comparison groups
    NNC0114-0006 v Placebo
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.0927
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.57
    Notes
    [2] - Due to the repeated analysis, the number of subjects included in the analysis were 148 and not only the 128 with an endpoint value at week 54.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Liraglutide/Placebo Ratio of week 54 to baseline are analysed using MMRM with an unstructured covariance matrix. Treatment, stratum and sex as factors and log baseline value and age as covariates, including the interaction between visit and all variables.
    Comparison groups
    Liraglutide v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 = 0.378
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment Ratio
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.42
    Notes
    [3] - Due to the repeated analysis, the number of subjects included in the analysis were 147 and not only the 131 with an endpoint value at week 54.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    NNC0114-0006 + liraglutide /NNC0114-0006 Ratio of week 54 to baseline are analysed using MMRM with an unstructured covariance matrix. Treatment, stratum and sex as factors and log baseline value and age as covariates, including the interaction between visit and all variables.
    Comparison groups
    NNC0114-0006 + Liraglutide v NNC0114-0006
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    P-value
    		 = 0.1377
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 1.53
    Notes
    [4] - Due to the repeated analysis, the number of subjects included in the analysis were 150 and not only the 131 with an endpoint value at week 54.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    NNC0114-0006 + liraglutide /Liraglutide. Ratio of week 54 to baseline are analysed using MMRM with an unstructured covariance matrix. Treatment, stratum and sex as factors and log baseline value and age as covariates, including the interaction between visit and all variables.
    Comparison groups
    NNC0114-0006 + Liraglutide v Liraglutide
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.0214
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatment ratio
    Point estimate
    1.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.69
    Notes
    [5] - Due to the repeated analysis, the number of subjects included in the analysis were 149 and not only the 134 with an endpoint value at week 54.
    Statistical analysis title
    		 Statistical analysis 6
    Statistical analysis description
    NNC0114-0006 /Liraglutide. Ratio of week 54 to baseline are analysed using MMRM with an unstructured covariance matrix. Treatment, stratum and sex as factors and log baseline value and age as covariates, including the interaction between visit and all variables.
    Comparison groups
    NNC0114-0006 v Liraglutide
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    P-value
    		 = 0.4187
    Method
    		 Mixed models analysis
    Parameter type
    		 Treatmrnt ratio
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.41
    Notes
    [6] - Due to the repeated analysis, the number of subjects included in the analysis were 149 and not only the 133 with an endpoint value at week 54.

    Secondary: Number of treatment emergent episodes of diabetic ketoacidosis (DKA)

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    End point title
    		 Number of treatment emergent episodes of diabetic ketoacidosis (DKA)
    End point description
    Number of treatment emergent episodes of diabetic ketoacidosis (DKA) from first dose of trial product to week 54
    End point type
    Secondary
    End point timeframe
    From first dose of trial product to week 54
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    77
    77
    76
    77
    Units: Number of episodes
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of treatment emergent hypoglycaemic episodes according to the American Diabetes Association (ADA) and Novo Nordisk definitions.

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    End point title
    		 Number of treatment emergent hypoglycaemic episodes according to the American Diabetes Association (ADA) and Novo Nordisk definitions.
    End point description
    Number of treatment emergent hypoglycaemic episodes according to the American Diabetes Association (ADA) and Novo Nordisk definitions, from first dose of trial product to week 54. ADA's definition of hypoglycaemia includes following categories: 1. Severe hypoglycaemia 2. Documented symptomatic hypoglycaemia 3. Asymptomatic hypoglycaemia 4. Probable symptomatic hypoglycaemia 5. Pseudo-hypoglycaemia. Novo Nordisk definition of Severe or BG confirmed hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.
    End point type
    Secondary
    End point timeframe
    From first dose of trial product to week 54
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    77
    77
    76
    77
    Units: Number of episodes
        American Diabetes Association (ADA)
    3354
    3420
    3224
    3411
        Novo Nordisk definitions
    577
    618
    479
    646
    No statistical analyses for this end point

    Secondary: AUC0-4h for MMTT stimulated C-peptide concentration time curve.

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    End point title
    		 AUC0-4h for MMTT stimulated C-peptide concentration time curve.
    End point description
    Area under the curve, from 0 to 4 hours (AUC0-4h) for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve at week 80 was measured as ratio to baseline value. C-peptide concentration was measured in unit 'nmol*h/L'.
    End point type
    Secondary
    End point timeframe
    At week 80 relative to baseline
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    63
    64
    62
    58
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.566 ± 71.3
    0.598 ± 70.2
    0.373 ± 115.8
    0.571 ± 100.9
    No statistical analyses for this end point

    Secondary: AUC0-2h for MMTT stimulated C-peptide concentration time curve (at week 54) relative to baseline

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    End point title
    		 AUC0-2h for MMTT stimulated C-peptide concentration time curve (at week 54) relative to baseline
    End point description
    Area under the curve, from 0 to 2 hours (AUC0-2h) for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve at week 54 was measured as ratio to baseline value. C-peptide concentration was measured in unit 'nmol*h/L'.
    End point type
    Secondary
    End point timeframe
    At week 54 relative to baseline
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    66
    65
    68
    63
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.961 ± 65.4
    0.824 ± 53.0
    0.646 ± 97.4
    0.655 ± 87.3
    No statistical analyses for this end point

    Secondary: AUC0-2h for MMTT stimulated C-peptide concentration time curve (at week 80) relative to baseline

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    End point title
    		 AUC0-2h for MMTT stimulated C-peptide concentration time curve (at week 80) relative to baseline
    End point description
    Area under the curve, from 0 to 2 hours (AUC0-2h) for a mixed meal tolerance test (MMTT) stimulated C-peptide concentration-time curve at week 80 was measured as ratio to baseline value. C-peptide concentration was measured in unit 'nmol*h/L'.
    End point type
    Secondary
    End point timeframe
    At week 80 relative to baseline
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    63
    64
    62
    58
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.590 ± 74.5
    0.619 ± 71.2
    0.370 ± 111.5
    0.540 ± 120.6
    No statistical analyses for this end point

    Secondary: Maximum MMTT stimulated C-peptide concentration (Cmax, C-peptide) (at week 54) relative to baseline

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    End point title
    		 Maximum MMTT stimulated C-peptide concentration (Cmax, C-peptide) (at week 54) relative to baseline
    End point description
    Maximum mixed meal tolerance test (MMTT) stimulated C-peptide concentration (Cmax, C-peptide) at week 54 was measured as ratio to baseline value. Cmax was measured in unit 'nmol/L'.
    End point type
    Secondary
    End point timeframe
    At week 54 relative to baseline
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    66
    65
    68
    63
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.978 ± 70.3
    0.779 ± 47.6
    0.733 ± 110.4
    0.644 ± 89.4
    No statistical analyses for this end point

    Secondary: Maximum MMTT stimulated C-peptide concentration (Cmax, C-peptide) (at week 80) relative to baseline

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    End point title
    		 Maximum MMTT stimulated C-peptide concentration (Cmax, C-peptide) (at week 80) relative to baseline
    End point description
    Maximum mixed meal tolerance test (MMTT) stimulated C-peptide concentration (Cmax, C-peptide) at week 80 was measured as ratio to baseline value. Cmax was measured in unit 'nmol/L'.
    End point type
    Secondary
    End point timeframe
    At week 80 relative to baseline
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    63
    64
    62
    58
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.580 ± 74.8
    0.592 ± 76.8
    0.389 ± 109.0
    0.568 ± 97.7
    No statistical analyses for this end point

    Secondary: Change in fasting C-peptide (from baseline to week 54)

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    End point title
    		 Change in fasting C-peptide (from baseline to week 54)
    End point description
    Change in fasting C-peptide at week 54 was measured as ratio to baseline value. C-peptide concentration was measured in unit 'nmol/L'.
    End point type
    Secondary
    End point timeframe
    From baseline to week 54
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    68
    64
    66
    64
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    1.01 ± 76.8
    0.70 ± 71.1
    0.65 ± 102.4
    0.66 ± 116.3
    No statistical analyses for this end point

    Secondary: Change in fasting C-peptide (from baseline to week 80)

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    End point title
    		 Change in fasting C-peptide (from baseline to week 80)
    End point description
    Change in fasting C-peptide at week 80 was measured as ratio to baseline value. C-peptide concentration was measured in unit 'nmol/L'.
    End point type
    Secondary
    End point timeframe
    From baseline to week 80
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    65
    63
    64
    60
    Units: Ratio
        geometric mean (geometric coefficient of variation)
    0.58 ± 112.9
    0.53 ± 106.2
    0.42 ± 132.5
    0.54 ± 154.4
    No statistical analyses for this end point

    Secondary: Change in HbA1c (from baseline to week 54)

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    End point title
    		 Change in HbA1c (from baseline to week 54)
    End point description
    Change in glycosylated haemoglobin (HbA1c) from baseline to week 54
    End point type
    Secondary
    End point timeframe
    From baseline to week 54
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    68
    65
    67
    65
    Units: percentage point
        arithmetic mean (standard deviation)
    -0.7 ± 1.9
    -0.5 ± 1.4
    -0.3 ± 1.5
    -0.3 ± 1.9
    No statistical analyses for this end point

    Secondary: Change in HbA1c (from baseline to week 80)

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    End point title
    		 Change in HbA1c (from baseline to week 80)
    End point description
    Change in glycosylated haemoglobin (HbA1c) from baseline to week 80
    End point type
    Secondary
    End point timeframe
    From baseline to week 80
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    66
    64
    68
    62
    Units: percentage point
        arithmetic mean (standard deviation)
    -0.1 ± 1.6
    -0.2 ± 1.5
    0.5 ± 2.1
    -0.4 ± 1.8
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (from baseline to week 54)

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    End point title
    		 Change in fasting plasma glucose (from baseline to week 54)
    End point description
    Change in fasting plasma glucose from baseline to week 54.
    End point type
    Secondary
    End point timeframe
    From baseline to week 54
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    66
    64
    66
    64
    Units: mmol/L
        arithmetic mean (standard deviation)
    0.5 ± 3.2
    0.2 ± 2.4
    -0.3 ± 3.1
    0.5 ± 2.4
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (from baseline to week 80)

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    End point title
    		 Change in fasting plasma glucose (from baseline to week 80)
    End point description
    Change in fasting plasma glucose from baseline to week 80
    End point type
    Secondary
    End point timeframe
    From baseline to week 80
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    62
    61
    65
    60
    Units: mmol/L
        arithmetic mean (standard deviation)
    1.1 ± 3.3
    0.3 ± 2.4
    0.2 ± 4.0
    1.0 ± 2.4
    No statistical analyses for this end point

    Secondary: Total daily insulin dose in units per kg (three day average) at week 54

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    End point title
    		 Total daily insulin dose in units per kg (three day average) at week 54
    End point description
    Total daily insulin dose in units per kg (three day average) at week 54
    End point type
    Secondary
    End point timeframe
    At week 54
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    56
    57
    62
    56
    Units: U/kg
        arithmetic mean (standard deviation)
    0.30 ± 0.19
    0.36 ± 0.22
    0.33 ± 0.23
    0.39 ± 0.23
    No statistical analyses for this end point

    Secondary: Total daily insulin dose in units per kg (three day average) at week 80

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    End point title
    		 Total daily insulin dose in units per kg (three day average) at week 80
    End point description
    Total daily insulin dose in units per kg (three day average) at week 80
    End point type
    Secondary
    End point timeframe
    At week 80
    End point values
    		 NNC0114-0006 + Liraglutide NNC0114-0006 Liraglutide Placebo
    Number of subjects analysed
    51
    57
    56
    51
    Units: U/kg
        arithmetic mean (standard deviation)
    0.46 ± 0.25
    0.40 ± 0.25
    0.45 ± 0.24
    0.44 ± 0.23
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Period from randomisation to end of trial (week 0 to week 80).
    Adverse event reporting additional description
    All reported adverse events are treatment-emergent.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21
    Reporting groups
    Reporting group title
    NNC0114-0006 + liraglutide
    Reporting group description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    NNC0114-0006
    Reporting group description
    		 Subjects received 12 mg/kg dose of NNC0114-0006 every 6 weeks, intravenously for 54 weeks. Subjects took liraglutide placebo once daily, subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    Liraglutide
    Reporting group description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. Subjects took 0.6 mg of liraglutide, subcutaneously, for first two weeks, 1.2 mg for next 2 weeks and 1.8 mg for rest of the treatment period. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received NNC0114-0006 placebo (volume equivalent to NNC0114-0006 dose of 12 mg/kg) every 6 weeks, intravenously for 54 weeks. In addition to that, subjects took liraglutide placebo once daily subcutaneously, with the volume of placebo equivalent to the volume liraglutide 0.6 mg, 1.2 mg and 1.8 mg. Subjects received treatment for 54 weeks followed by an off-treatment observation period of 26 weeks. Subjects continued their pre-trial insulin treatment throughout the trial.

    Serious adverse events
    		 NNC0114-0006 + liraglutide NNC0114-0006 Liraglutide Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 77 (9.09%)
    5 / 77 (6.49%)
    9 / 76 (11.84%)
    11 / 77 (14.29%)
         number of deaths (all causes)
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign soft tissue neoplasm
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Routine health maintenance
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Nasal polyps
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Cytomegalovirus test positive
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary contusion
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic shock
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Spinal muscular atrophy
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Headache
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic coma
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hypoglycaemic unconsciousness
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Haemorrhagic anaemia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoid tissue hyperplasia
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital herpes
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital herpes simplex
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    2 / 77 (2.60%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    2 / 77 (2.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 77 (1.30%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ketosis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 NNC0114-0006 + liraglutide NNC0114-0006 Liraglutide Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 77 (74.03%)
    55 / 77 (71.43%)
    62 / 76 (81.58%)
    54 / 77 (70.13%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 77 (2.60%)
    2 / 76 (2.63%)
    3 / 77 (3.90%)
         occurrences all number
    4
    2
    2
    3
    Blood immunoglobulin E increased
         subjects affected / exposed
    1 / 77 (1.30%)
    3 / 77 (3.90%)
    7 / 76 (9.21%)
    4 / 77 (5.19%)
         occurrences all number
    1
    3
    7
    5
    Lipase increased
         subjects affected / exposed
    5 / 77 (6.49%)
    1 / 77 (1.30%)
    1 / 76 (1.32%)
    2 / 77 (2.60%)
         occurrences all number
    6
    1
    1
    2
    Weight decreased
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 77 (2.60%)
    1 / 76 (1.32%)
    0 / 77 (0.00%)
         occurrences all number
    4
    2
    1
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    3 / 77 (3.90%)
         occurrences all number
    5
    2
    0
    3
    Skin laceration
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 77 (0.00%)
    0 / 76 (0.00%)
    4 / 77 (5.19%)
         occurrences all number
    0
    0
    0
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 77 (14.29%)
    10 / 77 (12.99%)
    10 / 76 (13.16%)
    11 / 77 (14.29%)
         occurrences all number
    21
    12
    11
    17
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 77 (5.19%)
    4 / 77 (5.19%)
    6 / 76 (7.89%)
    2 / 77 (2.60%)
         occurrences all number
    4
    4
    6
    4
    Pyrexia
         subjects affected / exposed
    3 / 77 (3.90%)
    7 / 77 (9.09%)
    7 / 76 (9.21%)
    4 / 77 (5.19%)
         occurrences all number
    4
    9
    12
    4
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 77 (2.60%)
    4 / 77 (5.19%)
    4 / 76 (5.26%)
    2 / 77 (2.60%)
         occurrences all number
    2
    5
    4
    4
    Abdominal distension
         subjects affected / exposed
    3 / 77 (3.90%)
    0 / 77 (0.00%)
    4 / 76 (5.26%)
    0 / 77 (0.00%)
         occurrences all number
    3
    0
    4
    0
    Abdominal pain
         subjects affected / exposed
    9 / 77 (11.69%)
    0 / 77 (0.00%)
    4 / 76 (5.26%)
    7 / 77 (9.09%)
         occurrences all number
    11
    0
    4
    10
    Abdominal pain upper
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    7 / 76 (9.21%)
    4 / 77 (5.19%)
         occurrences all number
    1
    0
    8
    6
    Diarrhoea
         subjects affected / exposed
    15 / 77 (19.48%)
    9 / 77 (11.69%)
    13 / 76 (17.11%)
    9 / 77 (11.69%)
         occurrences all number
    21
    15
    22
    11
    Dyspepsia
         subjects affected / exposed
    5 / 77 (6.49%)
    3 / 77 (3.90%)
    3 / 76 (3.95%)
    4 / 77 (5.19%)
         occurrences all number
    8
    6
    5
    4
    Nausea
         subjects affected / exposed
    19 / 77 (24.68%)
    6 / 77 (7.79%)
    42 / 76 (55.26%)
    9 / 77 (11.69%)
         occurrences all number
    33
    10
    62
    13
    Vomiting
         subjects affected / exposed
    14 / 77 (18.18%)
    0 / 77 (0.00%)
    17 / 76 (22.37%)
    4 / 77 (5.19%)
         occurrences all number
    24
    0
    34
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 77 (7.79%)
    4 / 77 (5.19%)
    5 / 76 (6.58%)
    1 / 77 (1.30%)
         occurrences all number
    7
    4
    7
    1
    Oropharyngeal pain
         subjects affected / exposed
    10 / 77 (12.99%)
    13 / 77 (16.88%)
    5 / 76 (6.58%)
    9 / 77 (11.69%)
         occurrences all number
    11
    18
    8
    11
    Respiratory disorder
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 77 (2.60%)
    0 / 76 (0.00%)
    5 / 77 (6.49%)
         occurrences all number
    4
    2
    0
    6
    Rhinorrhoea
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    2 / 76 (2.63%)
    4 / 77 (5.19%)
         occurrences all number
    1
    0
    4
    6
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 77 (0.00%)
    1 / 76 (1.32%)
    4 / 77 (5.19%)
         occurrences all number
    1
    0
    1
    6
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 77 (1.30%)
    1 / 76 (1.32%)
    3 / 77 (3.90%)
         occurrences all number
    4
    1
    1
    3
    Back pain
         subjects affected / exposed
    1 / 77 (1.30%)
    4 / 77 (5.19%)
    5 / 76 (6.58%)
    2 / 77 (2.60%)
         occurrences all number
    1
    6
    6
    3
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    3 / 77 (3.90%)
    6 / 77 (7.79%)
    5 / 76 (6.58%)
    4 / 77 (5.19%)
         occurrences all number
    4
    7
    6
    5
    Influenza
         subjects affected / exposed
    6 / 77 (7.79%)
    12 / 77 (15.58%)
    2 / 76 (2.63%)
    2 / 77 (2.60%)
         occurrences all number
    7
    14
    3
    2
    Nasopharyngitis
         subjects affected / exposed
    20 / 77 (25.97%)
    27 / 77 (35.06%)
    25 / 76 (32.89%)
    25 / 77 (32.47%)
         occurrences all number
    35
    63
    50
    45
    Pharyngitis
         subjects affected / exposed
    3 / 77 (3.90%)
    4 / 77 (5.19%)
    0 / 76 (0.00%)
    3 / 77 (3.90%)
         occurrences all number
    3
    5
    0
    4
    Respiratory tract infection viral
         subjects affected / exposed
    5 / 77 (6.49%)
    1 / 77 (1.30%)
    3 / 76 (3.95%)
    2 / 77 (2.60%)
         occurrences all number
    7
    1
    6
    2
    Rhinitis
         subjects affected / exposed
    5 / 77 (6.49%)
    3 / 77 (3.90%)
    3 / 76 (3.95%)
    5 / 77 (6.49%)
         occurrences all number
    5
    3
    5
    6
    Sinusitis
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 77 (2.60%)
    1 / 76 (1.32%)
    4 / 77 (5.19%)
         occurrences all number
    1
    5
    1
    4
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 77 (10.39%)
    5 / 77 (6.49%)
    4 / 76 (5.26%)
    7 / 77 (9.09%)
         occurrences all number
    13
    9
    4
    9
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    14 / 77 (18.18%)
    2 / 77 (2.60%)
    11 / 76 (14.47%)
    1 / 77 (1.30%)
         occurrences all number
    15
    2
    13
    1
    Hypoglycaemia
         subjects affected / exposed
    4 / 77 (5.19%)
    1 / 77 (1.30%)
    0 / 76 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    15
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Aug 2015
    Changes to protocol due to requirements from Voluntary Harmonisation Procedure (VHP).
    18 Apr 2016
    Reduction in number of subjects included in the full PK analysis. Updates to inclusion criteria and exclusion criteria.
    11 Nov 2016
    Flowchart updated Change in biomarker panel: Discontinued biomarkers: islet-specific auto reactive CD8+ and isotypes of GAD and IAA Newly added biomarker: Immune phenotyping of PBM
    23 May 2017
    Reinstatement of Visit 4 as a phone contact with only safety monitoring. Allowing use of Continuous Glucose Monitoring (CGM) and Flash Glucose Monitoring devices.
    26 Mar 2018
    Partial DBL added.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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