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    Clinical Trial Results:
    The efficacy and safety of liraglutide adjunct to insulin treatment in type 1 diabetes. A 26 week randomised, insulin capped, placebo-controlled, double-blind, parallel group, multinational, multi-centre trial

    Summary
    EudraCT number
    2012-005778-74
    Trial protocol
    AT   FI   BG   SE   IT   ES   BE   NL   DK   FR  
    Global end of trial date
    27 Apr 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    12 May 2016
    First version publication date
    12 May 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NN9211-4083
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02098395
    WHO universal trial number (UTN)
    U1111-1138-0619
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Allé, Bagsvaerd, Denmark, 2880
    Public contact
    Global Clinical Registry (GCR,1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
    Scientific contact
    Global Clinical Registry (GCR,1452), Novo Nordisk A/S, 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
    10 Dec 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Apr 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To confirm superiority of liraglutide compared to placebo, both adjunct to insulin treatment, on glycaemic control, after 26 weeks of treatment in subjects with established type 1 diabetes in inadequate glycaemic control.
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki (October 2013) and ICH Good Clinical Practice (May 1996) and 21 CFR 312.120.
    Background therapy
    Subjects continued their pre-trial insulin treatment (either basal bolus insulin treatment or continuous subcutaneous insulin infusion [CSII] treatment) throughout the trial. The type and brand of basal or bolus insulin was not to be changed (unless for safety of the subject) throughout the trial, as differences in insulin action and profiles could have the potential to interfere with the endpoints of the trial.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    08 May 2014
    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
    Netherlands: 27
    Country: Number of subjects enrolled
    Spain: 63
    Country: Number of subjects enrolled
    Sweden: 33
    Country: Number of subjects enrolled
    Austria: 40
    Country: Number of subjects enrolled
    Belgium: 64
    Country: Number of subjects enrolled
    Bulgaria: 54
    Country: Number of subjects enrolled
    Denmark: 32
    Country: Number of subjects enrolled
    Finland: 41
    Country: Number of subjects enrolled
    France: 41
    Country: Number of subjects enrolled
    Italy: 69
    Country: Number of subjects enrolled
    Canada: 57
    Country: Number of subjects enrolled
    United States: 267
    Country: Number of subjects enrolled
    South Africa: 47
    Worldwide total number of subjects
    835
    EEA total number of subjects
    464
    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)
    783
    From 65 to 84 years
    51
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were randomised at 113 sites in 13 countries: Austria 2 sites, Belgium 9 sites, Bulgaria 5 sites, Canada 9 sites, Denmark 4 sites, Finland 6 sites, France 9 sites, Italy 7 sites, Netherlands 5 sites, South Africa 2 sites, Spain 5 sites, Sweden 5 sites, United States 45 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
    Subjects were randomised to either liraglutide (0.6 mg, 1.2 mg or 1.8 mg) or placebo in a double-blinded manner; to preserve blinding, the dose volume ( 0.1 ml, 0.2 ml, 0.3 ml) in the liraglutide placebo groups were matched to the relevant active group (0.6 mg, 1.2 mg and 1.8 mg).

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Liraglutide 0.6 mg
    Arm description
    Subjects randomised to 0.6 mg liraglutide treatment as an add-on to their pre-trial insulin treatment and remained on this dose throughout the trial (26 weeks).
    Arm type
    Experimental

    Investigational medicinal product name
    Liraglutide
    Investigational medicinal product code
    Other name
    Victoza
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Liraglutide 0.6 mg, administered subcutaneously (s.c., under the skin) once daily.

    Arm title
    Liraglutide 1.2 mg
    Arm description
    Subjects randomised to 1.2 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Liraglutide
    Investigational medicinal product code
    Other name
    Victoza
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 24 weeks. Administered subcutaneously (s.c., under the skin) once daily.

    Arm title
    Liraglutide 1.8 mg
    Arm description
    Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects received 1.8 mg liraglutide for 22 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Liraglutide
    Investigational medicinal product code
    Other name
    Victoza
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects received 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

    Arm title
    Liraglutide placebo
    Arm description
    Subjects randomised to 3 different placebo arms as an add-on to their pre-trial insulin treatment. Administered subcutaneously (s.c., under the skin) once daily. All the 3 arms were pooled together for data analysis. a. Placebo 0.1 mL arm: Subjects received 0.1 mL placebo throughout the trial. b. Placebo 0.2 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 24 weeks. c. Placebo 0.3 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 2 weeks and 0.3 mL for next 22 weeks of the trial period.
    Arm type
    Placebo

    Investigational medicinal product name
    Liraglutide placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    a. Placebo 0.1 mL arm: Subjects received 0.1 mL placebo throughout the trial. b. Placebo 0.2 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 24 weeks. c. Placebo 0.3 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 2 weeks and 0.3 mL for next 22 weeks of the trial period.

    Number of subjects in period 1
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo
    Started
    212
    209
    207
    207
    Exposed
    211
    209
    206
    206
    Completed
    186
    177
    165
    180
    Not completed
    26
    32
    42
    27
         Protocol deviation
    2
    2
    -
    7
         Withdrawal by subject
    10
    10
    5
    13
         Adverse event, non-fatal
    12
    19
    34
    2
         Unclassified
    -
    -
    3
    2
         Lost to follow-up
    2
    1
    -
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Liraglutide 0.6 mg
    Reporting group description
    Subjects randomised to 0.6 mg liraglutide treatment as an add-on to their pre-trial insulin treatment and remained on this dose throughout the trial (26 weeks).

    Reporting group title
    Liraglutide 1.2 mg
    Reporting group description
    Subjects randomised to 1.2 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 24 weeks.

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects received 1.8 mg liraglutide for 22 weeks.

    Reporting group title
    Liraglutide placebo
    Reporting group description
    Subjects randomised to 3 different placebo arms as an add-on to their pre-trial insulin treatment. Administered subcutaneously (s.c., under the skin) once daily. All the 3 arms were pooled together for data analysis. a. Placebo 0.1 mL arm: Subjects received 0.1 mL placebo throughout the trial. b. Placebo 0.2 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 24 weeks. c. Placebo 0.3 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 2 weeks and 0.3 mL for next 22 weeks of the trial period.

    Reporting group values
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo Total
    Number of subjects
    212 209 207 207 835
    Age categorical
    Units: Subjects
    Age continuous
    Baseline age values were collected for full analysis set (FAS = 831 subjects). In FAS, number of subjects in liraglutide 0.6 mg arm was 211; number of subjects in liraglutide 1.2 mg arm was 209; number of subjects in liraglutide 1.8 mg arm was 205; number of subjects in liraglutide placebo arm was 206. Out of 835 randomised subjects, 4 were excluded from FAS: 1 subject each in the liraglutide 1.8 mg, 0.6 mg and placebo arm were not exposed to trial treatment and 1 subject in the liraglutide 1.8 mg arm had no post-baseline measurements.
    Units: years
        arithmetic mean (standard deviation)
    43.9 ± 12.88 42.8 ± 13.31 43.2 ± 12.9 42.7 ± 12.97 -
    Gender categorical
    Baseline gender data were collected for full analysis set (FAS = 831 subjects). In FAS, number of subjects in liraglutide 0.6 mg arm was 211; number of subjects in liraglutide 1.2 mg arm was 209; number of subjects in liraglutide 1.8 mg arm was 205; number of subjects in liraglutide placebo arm was 206. Out of 835 randomised subjects, 4 were excluded from FAS: 1 subject each in the liraglutide 1.8 mg, 0.6 mg and placebo arm were not exposed to trial treatment and 1 subject in the liraglutide 1.8 mg arm had no post-baseline measurements.
    Units: Subjects
        Female
    118 106 113 112 449
        Male
    93 103 92 94 382
        Not recorded
    1 0 2 1 4
    Glycosylated haemoglobin (HbA1c)
    Baseline HbA1c values were collected for full analysis set (FAS = 831 subjects). In FAS, number of subjects in liraglutide 0.6 mg arm was 211; number of subjects in liraglutide 1.2 mg arm was 209; number of subjects in liraglutide 1.8 mg arm was 205; number of subjects in liraglutide placebo arm was 206. Out of 835 randomised subjects, 4 were excluded from FAS: 1 subject each in the liraglutide 1.8 mg, 0.6 mg and placebo arm were not exposed to trial treatment and 1 subject in the liraglutide 1.8 mg arm had no post-baseline measurements.
    Units: Percent (%) glycosylated haemoglobin
        arithmetic mean (standard deviation)
    8.09 ± 0.743 8.07 ± 0.731 8.04 ± 0.736 8.12 ± 0.723 -
    Body weight
    Baseline body weight values were collected for full analysis set (FAS = 831 subjects). In FAS, number of subjects in liraglutide 0.6 mg arm was 211; number of subjects in liraglutide 1.2 mg arm was 209; number of subjects in liraglutide 1.8 mg arm was 205; number of subjects in liraglutide placebo arm was 206. Out of 835 randomised subjects, 4 were excluded from FAS: 1 subject each in the liraglutide 1.8 mg, 0.6 mg and placebo arm were not exposed to trial treatment and 1 subject in the liraglutide 1.8 mg arm had no post-baseline measurements.
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    83.1 ± 16.137 84.69 ± 18.155 83.64 ± 17.62 84.2 ± 16.539 -

    End points

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    End points reporting groups
    Reporting group title
    Liraglutide 0.6 mg
    Reporting group description
    Subjects randomised to 0.6 mg liraglutide treatment as an add-on to their pre-trial insulin treatment and remained on this dose throughout the trial (26 weeks).

    Reporting group title
    Liraglutide 1.2 mg
    Reporting group description
    Subjects randomised to 1.2 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 24 weeks.

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects received 1.8 mg liraglutide for 22 weeks.

    Reporting group title
    Liraglutide placebo
    Reporting group description
    Subjects randomised to 3 different placebo arms as an add-on to their pre-trial insulin treatment. Administered subcutaneously (s.c., under the skin) once daily. All the 3 arms were pooled together for data analysis. a. Placebo 0.1 mL arm: Subjects received 0.1 mL placebo throughout the trial. b. Placebo 0.2 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 24 weeks. c. Placebo 0.3 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 2 weeks and 0.3 mL for next 22 weeks of the trial period.

    Primary: Change from baseline in glycosylated haemoglobin (HbA1c)

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    End point title
    Change from baseline in glycosylated haemoglobin (HbA1c)
    End point description
    Change from baseline in glycosylated haemoglobin (HbA1c), after 26 weeks of treatment. Missing data imputed from a mixed model for repeated measurements with treatment, stratification and country as fixed factors and baseline value as a fixed covariate, all nested within visit. Full analysis set (FAS) included all randomised subjects who had received at least one dose and had any post-randomisation data (FAS = 831 subjects). Number subject analysed were subjects from FAS with available HbA1c data for week 26. Out of the 831 subjects in FAS, 22 subjects in lira 0.6 mg arm, 33 subjects in lira 1.2 mg arm, 35 subjects in lira 1.8 mg arm and 16 in placebo arm did not contribute to this analysis.
    End point type
    Primary
    End point timeframe
    After 26 weeks of treatment
    End point values
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo
    Number of subjects analysed
    189
    176
    170
    190
    Units: Percent (%) glycosylated haemoglobin
        arithmetic mean (standard deviation)
    -0.23 ± 0.744
    -0.23 ± 0.731
    -0.32 ± 0.73
    0.01 ± 0.674
    Statistical analysis title
    Statistical analysis 1
    Comparison groups
    Liraglutide 1.8 mg v Liraglutide placebo
    Number of subjects included in analysis
    360
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    < 0.0001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    -0.2
    Notes
    [1] - Superiority of liraglutide 1.8 mg versus placebo was planned to be concluded if and only if the upper limit of the two-sided 95% confidence interval for the estimated difference in HbA1c was less than zero.
    Statistical analysis title
    Statistical analysis 2
    Comparison groups
    Liraglutide 1.2 mg v Liraglutide placebo
    Number of subjects included in analysis
    366
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.0021
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.38
         upper limit
    -0.08
    Notes
    [2] - Superiority of liraglutide 1.2 mg was planned to be evaluated only if superiority for liraglutide 1.8 mg was concluded.
    Statistical analysis title
    Statistical analysis 3
    Comparison groups
    Liraglutide 0.6 mg v Liraglutide placebo
    Number of subjects included in analysis
    379
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.0011
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.39
         upper limit
    -0.1
    Notes
    [3] - Superiority of liraglutide 0.6 mg versus placebo was planned to be evaluated only if superiority of liraglutide 1.2 mg was concluded.

    Secondary: Change from baseline in body weight

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    End point title
    Change from baseline in body weight
    End point description
    Change from baseline in body weight after 26 weeks of treatment. Missing data imputed from a mixed model for repeated measurements with treatment, stratification and country as fixed factors and baseline value as a fixed covariate, all nested within visit. Full analysis set (FAS) included all randomised subjects who had received at least one dose and had any post-randomisation data (FAS = 831 subjects). Number subject analysed were subjects from FAS with available body weight data for week 26. Out of the 831 subjects in FAS, 27 subjects in lira 0.6 mg arm, 38 subjects in lira 1.2 mg arm, 35 subjects in lira 1.8 mg arm and 26 in placebo arm did not contribute to the analysis.
    End point type
    Secondary
    End point timeframe
    After 26 weeks of treatment
    End point values
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo
    Number of subjects analysed
    184
    171
    170
    180
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    -2.37 ± 3.015
    -4.03 ± 3.677
    -5.1 ± 3.787
    -0.26 ± 2.782
    No statistical analyses for this end point

    Secondary: Number of treatment-emergent symptomatic hypoglycaemic episodes

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    End point title
    Number of treatment-emergent symptomatic hypoglycaemic episodes
    End point description
    Number of treatment-emergent symptomatic hypoglycaemic episodes during 26 weeks of treatment. Symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or a self measured plasma glucose (SMPG) value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia. Safety analysis set (SAS) included all subjects exposed to at least one dose of randomised liraglutide or placebo (SAS = 832 subjects). Severe hypoglycaemia as per ADA classification is defined as an episode that required assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. Plasma glucose (PG) concentration may not have been available during an event, but neurological recovery following the return of PG to normal was considered sufficient evidence that the event was induced by a low PG concentration.
    End point type
    Secondary
    End point timeframe
    During 26 weeks of treatment
    End point values
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo
    Number of subjects analysed
    211 [4]
    209 [5]
    206 [6]
    206 [7]
    Units: Number of episodes
    1437
    1943
    1490
    1567
    Notes
    [4] - 1437 episodes of symptomatic hypoglycaemia were reported by 166 subjects.
    [5] - 1943 episodes of symptomatic hypoglycaemia were reported by 175 subjects.
    [6] - 1490 episodes of symptomatic hypoglycaemia were reported by 160 subjects.
    [7] - 1567 episodes of symptomatic hypoglycaemia were reported by 162 subjects.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first day of exposure (week 0) to randomised treatment to 7 days after the last day of randomised treatment (week 26).
    Adverse event reporting additional description
    Safety analysis set (SAS) included all subjects exposed to at least one dose of randomised liraglutide or placebo.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Liraglutide 0.6 mg
    Reporting group description
    Subjects randomised to 0.6 mg liraglutide treatment as an add-on to their pre-trial insulin treatment and remained on this dose throughout the trial (26 weeks).

    Reporting group title
    Liraglutide 1.2 mg
    Reporting group description
    Subjects randomised to 1.2 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 24 weeks.

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment received 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects received 1.8 mg liraglutide for 22 weeks.

    Reporting group title
    Liraglutide placebo
    Reporting group description
    Subjects randomised to 3 different placebo arms as an add-on to their pre-trial insulin treatment. Administered subcutaneously (s.c., under the skin) once daily. All the 3 arms were pooled together for data analysis. a. Placebo 0.1 mL arm: Subjects received 0.1 mL placebo throughout the trial. b. Placebo 0.2 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 24 weeks. c. Placebo 0.3 mL arm: Subjects received 0.1 mL placebo for 2 weeks followed by 0.2 mL for 2 weeks and 0.3 mL for next 22 weeks of the trial period.

    Serious adverse events
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 211 (9.48%)
    21 / 209 (10.05%)
    14 / 206 (6.80%)
    14 / 206 (6.80%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Surgical and medical procedures
    Wrist surgery
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Uterine leiomyoma
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Chest pain
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Depressed mood
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Depression
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Reproductive system and breast disorders
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Foot fracture
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Forearm fracture
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Intervertebral disc injury
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Joint dislocation
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Ligament sprain
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Meniscus injury
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Tibia fracture
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Coronary artery disease
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    2 / 206 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Myocardial ischaemia
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Respiratory distress
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Hypoglycaemic coma
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Hypoglycaemic unconsciousness
         subjects affected / exposed
    3 / 211 (1.42%)
    6 / 209 (2.87%)
    2 / 206 (0.97%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    1 / 5
    5 / 7
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Syncope
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Transient ischaemic attack
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    VIth nerve paralysis
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 211 (0.00%)
    2 / 209 (0.96%)
    0 / 206 (0.00%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Vomiting
         subjects affected / exposed
    0 / 211 (0.00%)
    2 / 209 (0.96%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Diabetic nephropathy
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Nephrolithiasis
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    1 / 206 (0.49%)
    0 / 206 (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
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Cholecystitis
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    0 / 206 (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
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 211 (0.47%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    2 / 206 (0.97%)
    2 / 206 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Hypoglycaemia
         subjects affected / exposed
    5 / 211 (2.37%)
    2 / 209 (0.96%)
    1 / 206 (0.49%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    4 / 6
    2 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Gastroenteritis
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    0 / 206 (0.00%)
    0 / 206 (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
    Pneumonia
         subjects affected / exposed
    0 / 211 (0.00%)
    1 / 209 (0.48%)
    1 / 206 (0.49%)
    0 / 206 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 211 (0.47%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 211 (0.00%)
    0 / 209 (0.00%)
    0 / 206 (0.00%)
    1 / 206 (0.49%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Liraglutide placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    137 / 211 (64.93%)
    164 / 209 (78.47%)
    162 / 206 (78.64%)
    125 / 206 (60.68%)
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    10 / 211 (4.74%)
    4 / 209 (1.91%)
    14 / 206 (6.80%)
    6 / 206 (2.91%)
         occurrences all number
    12
    4
    19
    10
    Nervous system disorders
    Headache
         subjects affected / exposed
    16 / 211 (7.58%)
    26 / 209 (12.44%)
    30 / 206 (14.56%)
    30 / 206 (14.56%)
         occurrences all number
    27
    33
    43
    40
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    13 / 211 (6.16%)
    17 / 209 (8.13%)
    22 / 206 (10.68%)
    3 / 206 (1.46%)
         occurrences all number
    13
    18
    25
    5
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    3 / 211 (1.42%)
    14 / 209 (6.70%)
    7 / 206 (3.40%)
    6 / 206 (2.91%)
         occurrences all number
    4
    18
    7
    7
    Abdominal pain upper
         subjects affected / exposed
    8 / 211 (3.79%)
    8 / 209 (3.83%)
    14 / 206 (6.80%)
    5 / 206 (2.43%)
         occurrences all number
    8
    13
    17
    5
    Constipation
         subjects affected / exposed
    6 / 211 (2.84%)
    23 / 209 (11.00%)
    14 / 206 (6.80%)
    9 / 206 (4.37%)
         occurrences all number
    6
    29
    15
    12
    Diarrhoea
         subjects affected / exposed
    14 / 211 (6.64%)
    25 / 209 (11.96%)
    30 / 206 (14.56%)
    17 / 206 (8.25%)
         occurrences all number
    17
    30
    43
    22
    Dyspepsia
         subjects affected / exposed
    8 / 211 (3.79%)
    19 / 209 (9.09%)
    24 / 206 (11.65%)
    1 / 206 (0.49%)
         occurrences all number
    9
    23
    35
    1
    Nausea
         subjects affected / exposed
    68 / 211 (32.23%)
    97 / 209 (46.41%)
    102 / 206 (49.51%)
    34 / 206 (16.50%)
         occurrences all number
    81
    122
    170
    40
    Vomiting
         subjects affected / exposed
    19 / 211 (9.00%)
    29 / 209 (13.88%)
    35 / 206 (16.99%)
    7 / 206 (3.40%)
         occurrences all number
    25
    40
    65
    8
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 211 (1.42%)
    5 / 209 (2.39%)
    8 / 206 (3.88%)
    14 / 206 (6.80%)
         occurrences all number
    4
    6
    10
    15
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    21 / 211 (9.95%)
    40 / 209 (19.14%)
    50 / 206 (24.27%)
    9 / 206 (4.37%)
         occurrences all number
    21
    42
    55
    10
    Hyperglycaemia
         subjects affected / exposed
    10 / 211 (4.74%)
    13 / 209 (6.22%)
    12 / 206 (5.83%)
    4 / 206 (1.94%)
         occurrences all number
    14
    17
    16
    4
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    6 / 211 (2.84%)
    11 / 209 (5.26%)
    8 / 206 (3.88%)
    6 / 206 (2.91%)
         occurrences all number
    7
    11
    9
    6
    Influenza
         subjects affected / exposed
    15 / 211 (7.11%)
    18 / 209 (8.61%)
    18 / 206 (8.74%)
    17 / 206 (8.25%)
         occurrences all number
    15
    23
    19
    20
    Nasopharyngitis
         subjects affected / exposed
    44 / 211 (20.85%)
    40 / 209 (19.14%)
    47 / 206 (22.82%)
    46 / 206 (22.33%)
         occurrences all number
    59
    52
    67
    56
    Sinusitis
         subjects affected / exposed
    7 / 211 (3.32%)
    11 / 209 (5.26%)
    3 / 206 (1.46%)
    4 / 206 (1.94%)
         occurrences all number
    7
    12
    3
    4
    Upper respiratory tract infection
         subjects affected / exposed
    14 / 211 (6.64%)
    11 / 209 (5.26%)
    11 / 206 (5.34%)
    25 / 206 (12.14%)
         occurrences all number
    20
    13
    14
    31

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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