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    Clinical Trial Results:
    Evaluation of Insuman Implantable 400 IU/ml in Patients with Type 1 Diabetes Treated with the Medtronic MiniMed Implantable Pump System Using Insuplant 400 IU/mL

    Summary
    EudraCT number
    2010-021373-37
    Trial protocol
    FR   NL   SE   BE  
    Global end of trial date
    01 Feb 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    14 Feb 2019
    First version publication date
    14 Feb 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    HUBIN_L_05335
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01194882
    WHO universal trial number (UTN)
    U1111-1116-7658
    Other trial identifiers
    STUDY NAME: HUBIN
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Jan 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Feb 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare Insuman Implantable 400 International Units (IU)/ml versus Insuplant 400 IU/ml with respect to the pump refill accuracy during a 4 refill cycle period (comparative phase = 160±20 days); To assess efficacy measured by haemoglobin glycosylated (HBA1c) change in Insuman Implantable 400 IU/ml group versus Insuplant 400 IU/ml group after a 4 refill cycle period (comparative phase = 160±20 days).
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    16 Nov 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 75
    Country: Number of subjects enrolled
    Sweden: 29
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    France: 365
    Worldwide total number of subjects
    472
    EEA total number of subjects
    472
    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)
    2
    Adults (18-64 years)
    403
    From 65 to 84 years
    67
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 17 sites in 4 countries between 16 November 2010 and 01 February 2018. A total of 472 subjects were included in study which consisted of 3 phases: comparative phase, non-comparative phase and treatment phase with Insuman Implantable.

    Pre-assignment
    Screening details
    Of 472 subjects, 169 subjects were randomized in 1:1 ratio (Insuman Implantable : Insuplant) in comparative phase & 307 were included in non-comparative and treatment phase with Insuman Implantable. i.e. out of the included subjects, two-third subjects participated in two phases and one-third participated only in the Insuman non-comparative phase.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Single blind
    Roles blinded
    Subject

    Arms
    Arm title
    All Subjects
    Arm description
    Subjects earlier treated with Insuplant 400 International Units Per Millilitre (IU/mL) were included in the study and received Insuman Implantable 400 IU/mL or Insuplant IU/mL for 4 refill cycles in comparative phase and Insuplant 400 IU/mL for 4 refill cycles as per standard care in non-comparative phase. Comparative phase was followed by a treatment phase with only Insuman Implantable 400 IU/mL until its availability on the market. Each pump refill cycle was 40±5 days.
    Arm type
    Experimental

    Investigational medicinal product name
    Insuman Implantable
    Investigational medicinal product code
    Other name
    Human insulin (rapid acting)
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intraperitoneal use
    Dosage and administration details
    The glucose targets and insulin dose were established by the Investigator on a subject basis and as per American Diabetes Association guidelines. Treatments was administered by Continuous IntraPeritoneal Insulin Infusion (CIPII) through an implantable pump system.

    Investigational medicinal product name
    Insuplant
    Investigational medicinal product code
    Other name
    Human insulin semi synthetic porcine derived
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intraperitoneal use
    Dosage and administration details
    The glucose targets and insulin dose were established by the Investigator on a subject basis and as per American Diabetes Association guidelines. Treatments was administered by CIPII through an implantable pump system.

    Number of subjects in period 1
    All Subjects
    Started
    472
    Completed
    356
    Not completed
    116
         Lack of efficacy
             6
         Other than specified above
             26
         Consent withdrawn by subject
             18
         Adverse Event
             65
         Lost to follow-up
             1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    All Subjects
    Reporting group description
    Subjects earlier treated with Insuplant 400 International Units Per Millilitre (IU/mL) were included in the study and received Insuman Implantable 400 IU/mL or Insuplant IU/mL for 4 refill cycles in comparative phase and Insuplant 400 IU/mL for 4 refill cycles as per standard care in non-comparative phase. Comparative phase was followed by a treatment phase with only Insuman Implantable 400 IU/mL until its availability on the market. Each pump refill cycle was 40±5 days.

    Reporting group values
    All Subjects Total
    Number of subjects
    472 472
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    50.18 ± 12.82 -
    Gender categorical
    Units: Subjects
        Female
    298 298
        Male
    174 174
    Baseline HbA1c
    Data for baseline HbA1c is reported for 365 subjects.
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    7.96 ± 1.28 -
    Actual Baseline Insulin Dose
    Data for actual baseline insulin dose is reported for 223 subjects.
    Units: IU/day
        arithmetic mean (standard deviation)
    49.90 ± 25.96 -

    End points

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    End points reporting groups
    Reporting group title
    All Subjects
    Reporting group description
    Subjects earlier treated with Insuplant 400 International Units Per Millilitre (IU/mL) were included in the study and received Insuman Implantable 400 IU/mL or Insuplant IU/mL for 4 refill cycles in comparative phase and Insuplant 400 IU/mL for 4 refill cycles as per standard care in non-comparative phase. Comparative phase was followed by a treatment phase with only Insuman Implantable 400 IU/mL until its availability on the market. Each pump refill cycle was 40±5 days.

    Subject analysis set title
    Insuman (Comparative Phase)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Subjects received Insuman Implantable 400 IU/mL for 4 refill cycles i.e. 6 Months by continuous intraperitoneal insulin infusion through an implantable pump system.

    Subject analysis set title
    Insuplant (Comparative Phase)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Subjects received Insuplant 400 IU/mL for 4 refill cycles i.e. 6 Months by continuous intraperitoneal insulin infusion through an implantable pump system.

    Subject analysis set title
    Insuplant Phase
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Subjects (who were not included in comparative phase) received Insuplant 400 IU/mL for 4 refill cycles as per standard care by continuous intraperitoneal insulin infusion through an implantable pump system.

    Subject analysis set title
    Insuman Phase
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Subjects received Insuman 400 IU/mL for 4 refill cycles as per standard care by continuous intraperitoneal insulin infusion through an implantable pump system and avoided pump ex-plantation.

    Primary: Percentage Refill Accuracy After 4 Refill Cycles: Modified Intent to Treat (mITT) Population

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    End point title
    Percentage Refill Accuracy After 4 Refill Cycles: Modified Intent to Treat (mITT) Population
    End point description
    Refill accuracy was calculated as a percentage difference between the theoretical refill volume calculated by the personal pump communicator (PPC) using programmed values and the actual refill volume used by weight measurement after 4 refill cycles. Analysis was performed on mITT population for refill accuracy. mITT population included subjects who had given their informed consent, for whom there was confirmation of successful allocation of a randomization number through the study treatment allocation system, and who received at least one administration of the study drug and had an evaluation for each primary outcome. Subjects who had no available or no valid post-baseline refill value were excluded from the mITT population for refill accuracy.
    End point type
    Primary
    End point timeframe
    From baseline up to refill cycle 4 (i.e. Month 6)
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    66
    64
    Units: percentage accuracy
        arithmetic mean (standard deviation)
    0.06 ± 8.00
    2.82 ± 5.91
    Statistical analysis title
    Comparative Phase: Insuman vs Insuplant
    Statistical analysis description
    Analysis was performed using Analysis of variance (ANOVA) method.
    Comparison groups
    Insuman (Comparative Phase) v Insuplant (Comparative Phase)
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    P-value
    = 0.0273
    Method
    ANOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -2.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.21
         upper limit
    -0.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.24
    Notes
    [1] - Non-inferiority of Insuman Implantable over Insuplant was demonstrated if upper limit of 2-sided 95% confidence interval (CI) of the intergroup difference was <5%.

    Primary: Percentage Refill Accuracy After 4 Refill Cycles: Per Protocol (PP) Population

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    End point title
    Percentage Refill Accuracy After 4 Refill Cycles: Per Protocol (PP) Population
    End point description
    Refill accuracy was calculated as a percentage difference between the theoretical refill volume calculated by the PPC using programmed values and the actual refill volume used by weight measurement after 4 refill cycles. Analysis was performed on PP population for refill accuracy. PP population was a subset of mITT population without major protocol violations for each primary parameter.
    End point type
    Primary
    End point timeframe
    From baseline up to refill cycle 4 (i.e. Month 6)
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    62
    56
    Units: percentage accuracy
        arithmetic mean (standard deviation)
    -0.08 ± 8.14
    3.07 ± 6.17
    Statistical analysis title
    Comparative Phase: Insuman vs Insuplant
    Statistical analysis description
    Analysis was performed using ANOVA method.
    Comparison groups
    Insuman (Comparative Phase) v Insuplant (Comparative Phase)
    Number of subjects included in analysis
    118
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    P-value
    = 0.0205
    Method
    ANOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -3.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.81
         upper limit
    -0.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.34
    Notes
    [2] - Non-inferiority of Insuman Implantable over Insuplant was demonstrated if upper limit of 2-sided 95% confidence interval (CI) of the intergroup difference was <5%.

    Primary: Change From Baseline in HbA1c to Month 6: mITT Population

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    End point title
    Change From Baseline in HbA1c to Month 6: mITT Population
    End point description
    Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Analysis was performed on mITT population for HbA1c.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    84
    84
    Units: percentage of HbA1c
        arithmetic mean (standard deviation)
    -0.27 ± 0.70
    -0.20 ± 0.79
    Statistical analysis title
    Comparative Phase: Insuman vs Insuplant
    Statistical analysis description
    Analysis was performed using ANOVA method.
    Comparison groups
    Insuplant (Comparative Phase) v Insuman (Comparative Phase)
    Number of subjects included in analysis
    168
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    P-value
    = 0.543
    Method
    ANOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [3] - Non-inferiority of Insuman Implantable over Insuplant was demonstrated if upper limit of 2-sided 95% CI of the inter group difference was 0.4%.

    Primary: Change From Baseline in HbA1c to Month 6: PP Population

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    End point title
    Change From Baseline in HbA1c to Month 6: PP Population
    End point description
    Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Analysis was performed on PP population for HbA1c.
    End point type
    Primary
    End point timeframe
    Baseline, Month 6
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    75
    69
    Units: percentage of HbA1c
        arithmetic mean (standard deviation)
    -0.25 ± 0.67
    -0.12 ± 0.74
    Statistical analysis title
    Comparative Phase: Insuman vs Insuplant
    Statistical analysis description
    Analysis was performed using ANOVA method.
    Comparison groups
    Insuman (Comparative Phase) v Insuplant (Comparative Phase)
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    P-value
    = 0.2808
    Method
    ANOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.36
         upper limit
    0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Notes
    [4] - Non-inferiority of Insuman Implantable over Insuplant was demonstrated if upper limit of 2-sided 95% CI of the inter group difference was 0.4%.

    Secondary: Actual Daily Insulin Dose at Month 6: mITT Population

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    End point title
    Actual Daily Insulin Dose at Month 6: mITT Population
    End point description
    Actual daily insulin doses were calculated at each refill from actual amount used after conversion in International Units (IU), and reported to the time between the refill and the previous refill in days. Analysis was performed on mITT population for HbA1c. Here "number analyzed" signifies number of subjects with available data for this end point.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    61
    61
    Units: IU/day
        arithmetic mean (standard deviation)
    56.72 ± 23.16
    54.30 ± 22.86
    No statistical analyses for this end point

    Secondary: Actual Daily Insulin Dose at Month 6: PP Population

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    End point title
    Actual Daily Insulin Dose at Month 6: PP Population
    End point description
    Actual daily insulin doses were calculated at each refill from actual amount used after conversion in IU, and reported to the time between the refill and the previous refill in days. Analysis was performed on PP population for HbA1c. Here "number analyzed" signifies number of subjects with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    57
    53
    Units: IU/day
        arithmetic mean (standard deviation)
    56.24 ± 21.57
    55.80 ± 23.68
    No statistical analyses for this end point

    Secondary: Number of Subjects With At Least One Severe Hypoglycemic Events

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    End point title
    Number of Subjects With At Least One Severe Hypoglycemic Events
    End point description
    Severe hypoglycemia was an event in which the subject required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Diurnal (day-time) hypoglycaemia occurring during the waking period and nocturnal hypoglycaemia, which occurred while the subject was asleep, after bedtime and before getting up in the morning. Analysis was performed on safety population composed of all randomized subjects exposed to the study drug, i.e. who received at least one administration of the study drug.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Month 6
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    84
    84
    Units: subjects
    number (not applicable)
        At least one severe hypoglycaemia
    12
    11
        At least one nocturnal severe hypoglycaemia
    1
    3
        At least one diurnal severe hypoglycaemia
    10
    8
    No statistical analyses for this end point

    Secondary: Number of Subjects With At Least One Hyperglycemia With Ketonemia

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    End point title
    Number of Subjects With At Least One Hyperglycemia With Ketonemia
    End point description
    Hyperglycaemia is defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical, dietary or insulin dosage reason. Subjects with at least one hyperglycaemia with ketonemia and ketonemia > 0.5 mmol/l were reported. Analysis was performed on safety population.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Month 6
    End point values
    Insuman (Comparative Phase) Insuplant (Comparative Phase)
    Number of subjects analysed
    84
    84
    Units: subjects
    number (not applicable)
        At least one hyperglycaemia with ketonemia
    13
    15
        At least 1 hyperglycaemia with ketonemia>0.5mmol/l
    2
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All Adverse Events (AEs) were collected from signature of informed consent form until the end of the study i.e. end of Insuman non comparative phase (maximum treatment exposure: 6.6 years) regardless of seriousness/relationship to investigational product.
    Adverse event reporting additional description
    Reported AEs & deaths are treatment-emergent AEs that is AEs that developed/worsened & deaths occurred during ‘on treatment period’ (time interval between first Insuman administration & 10 days after last study drug administration).Safety population. 3 subjects from comparative phase(1 from Insuman & 2 from Insuplant) were not included in analysis.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Insuman comparative phase
    Reporting group description
    Subjects received Insuman Implantable 400 IU/mL for 4 refill cycles i.e. 6 Months by continuous intraperitoneal insulin infusion through an implantable pump system (Medtronic Minimed implantable pump). Out of 84 subjects, 1 subject was not included in safety population.

    Reporting group title
    Insuplant comparative phase
    Reporting group description
    Subjects received Insuplant 400 IU/mL for 4 refill cycles i.e. 6 Months by continuous intraperitoneal insulin infusion through an implantable pump system (Medtronic Minimed implantable pump). Out of 84 subjects, 2 subjects were not included in safety population.

    Reporting group title
    Insuplant phase
    Reporting group description
    Subjects who were not included in comparative phase, received Insuplant 400 IU/mL for 4 refill cycles as per standard care by continuous intraperitoneal insulin infusion through an implantable pump system (Medtronic Minimed implantable pump).

    Reporting group title
    Insuman phase
    Reporting group description
    Subjects received Insuman 400 IU/mL for 4 refill cycles as per standard care by continuous intraperitoneal insulin infusion through an implantable pump system (Medtronic Minimed implantable pump) and avoided pump ex-plantation.

    Serious adverse events
    Insuman comparative phase Insuplant comparative phase Insuplant phase Insuman phase
    Total subjects affected by serious adverse events
         subjects affected / exposed
    64 / 83 (77.11%)
    61 / 82 (74.39%)
    113 / 159 (71.07%)
    101 / 148 (68.24%)
         number of deaths (all causes)
    1
    2
    3
    5
         number of deaths resulting from adverse events
    Vascular disorders
    Adventitial Cystic Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Arterial Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Arterial Insufficiency
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Arterial Occlusive Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Arteriosclerosis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Arteritis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Embolism Venous
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Hypertension
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Intermittent Claudication
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Orthostatic Hypotension
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Peripheral Arterial Occlusive Disease
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Artery Occlusion
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Peripheral Artery Stenosis
         subjects affected / exposed
    2 / 83 (2.41%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Ischaemia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    0 / 148 (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
    Phlebitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Superior Vena Cava Stenosis
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Surgical and medical procedures
    Arterial Therapeutic Procedure
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Breast Prosthesis Implantation
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Caesarean Section
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Cataract Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystectomy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Coronary Angioplasty
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Coronary Artery Bypass
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Coronary Revascularisation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Cyst Removal
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Finger Repair Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Gastric Bypass
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Hospitalisation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Hysterectomy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Leg Amputation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Mammoplasty
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical Device Change
         subjects affected / exposed
    3 / 83 (3.61%)
    7 / 82 (8.54%)
    11 / 159 (6.92%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    3 / 4
    8 / 8
    10 / 11
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical Device Implantation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Medical Device Removal
         subjects affected / exposed
    1 / 83 (1.20%)
    3 / 82 (3.66%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 3
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian Cystectomy
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Pancreas Transplant
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Percutaneous Coronary Intervention
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Peripheral Nerve Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Peripheral Revascularisation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Prostatic Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Renal Sympathetic Nerve Ablation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Renal Transplant
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Retinal Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Rotator Cuff Repair
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Sinus Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Stent Placement
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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 Vascular Shunt
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Tendon Operation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Toe Amputation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Transplant
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Bladder Cancer
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Breast Cancer
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    3 / 159 (1.89%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Neoplasm
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Hodgkin's Disease Lymphocyte Depletion Type Stage Iii
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Intestinal Adenocarcinoma
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Meningioma
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Metastatic Gastric Cancer
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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 / 1
    Prostate Cancer
         subjects affected / exposed
    2 / 83 (2.41%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Cancer
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Squamous Cell Carcinoma
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Immune system disorders
    Amyloidosis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Anaphylactic Shock
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Insulin Autoimmune Syndrome
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Delivery
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Live Birth
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Pre-Eclampsia
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Pregnancy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Unintended Pregnancy
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    0 / 148 (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
    Catheter Site Pain
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Chest Pain
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General Physical Health Deterioration
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Generalised Oedema
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Granuloma
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Impaired Healing
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Malaise
         subjects affected / exposed
    2 / 83 (2.41%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical Device Site Atrophy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Medical Device Site Erosion
         subjects affected / exposed
    2 / 83 (2.41%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical Device Site Erythema
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Medical Device Site Haemorrhage
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical Device Site Inflammation
         subjects affected / exposed
    3 / 83 (3.61%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical Device Site Pain
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    11 / 148 (7.43%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    10 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Oedema Due To Cardiac Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Oedema Peripheral
         subjects affected / exposed
    2 / 83 (2.41%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prolapse
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Pyrexia
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden Death
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Swelling
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Depression
         subjects affected / exposed
    3 / 83 (3.61%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Major Depression
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Mania
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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 Decompensation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Sleep Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Suicidal Ideation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Suicide Attempt
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast Enlargement
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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 Prolapse
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Haemorrhagic Ovarian Cyst
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Menometrorrhagia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Metrorrhagia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Ovarian Cyst
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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 Polyp
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Injury, poisoning and procedural complications
    Abdominal Wall Wound
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Accidental Exposure To Product
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Accidental Overdose
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Acetabulum Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Animal Bite
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         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
    Ankle Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    0 / 148 (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
    Complications Of Transplanted Pancreas
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Concussion
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Electric Shock
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Fall
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    3 / 159 (1.89%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Femur Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    3 / 159 (1.89%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Humerus Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint Dislocation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Ligament Sprain
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Limb Injury
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Lower Limb Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Procedural Nausea
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pubis Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Road Traffic Accident
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scapula Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Scar
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Skin Injury
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Subarachnoid Haemorrhage
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Subdural Haematoma
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Thoracic Vertebral Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Tibia Fracture
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Ulna Fracture
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Upper Limb Fracture
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Vth Nerve Injury
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Wound Dehiscence
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Wrist Fracture
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Investigations
    Blood Glucose Fluctuation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Blood Glucose Increased
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular Evaluation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Heart Rate Increased
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Laparoscopy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Medical Observation
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight Increased
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Acute Coronary Syndrome
         subjects affected / exposed
    2 / 83 (2.41%)
    1 / 82 (1.22%)
    2 / 159 (1.26%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    2 / 83 (2.41%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic Valve Stenosis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         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
    Atrial Fibrillation
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiac Arrest
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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 Failure
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Cardiovascular Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Coronary Artery Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    0 / 148 (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
    Coronary Artery Stenosis
         subjects affected / exposed
    2 / 83 (2.41%)
    1 / 82 (1.22%)
    3 / 159 (1.89%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic Cardiomyopathy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Myocardial Infarction
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Tachycardia
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Respiratory, thoracic and mediastinal disorders
    Acute Pulmonary Oedema
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Asthma
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Dyspnoea
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea Exertional
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Epistaxis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Haemoptysis
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary Oedema
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep Apnoea Syndrome
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Microcytic Anaemia
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Pernicious Anaemia
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Nervous system disorders
    Balance Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Carotid Artery Stenosis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Carpal Tunnel Syndrome
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    3 / 159 (1.89%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    1 / 83 (1.20%)
    2 / 82 (2.44%)
    3 / 159 (1.89%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Epilepsy
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Extrapyramidal Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Headache
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic Coma
         subjects affected / exposed
    8 / 83 (9.64%)
    5 / 82 (6.10%)
    8 / 159 (5.03%)
    6 / 148 (4.05%)
         occurrences causally related to treatment / all
    6 / 26
    1 / 6
    4 / 13
    3 / 13
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Hypoglycaemic Seizure
         subjects affected / exposed
    3 / 83 (3.61%)
    2 / 82 (2.44%)
    2 / 159 (1.26%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    1 / 5
    2 / 2
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic Unconsciousness
         subjects affected / exposed
    6 / 83 (7.23%)
    2 / 82 (2.44%)
    13 / 159 (8.18%)
    6 / 148 (4.05%)
         occurrences causally related to treatment / all
    1 / 17
    1 / 2
    5 / 19
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar Stroke
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Loss Of Consciousness
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Nerve Compression
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Neuralgia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Presyncope
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Seizure
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         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
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    3 / 83 (3.61%)
    3 / 82 (3.66%)
    2 / 159 (1.26%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic Retinopathy
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal Aneurysm
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Retinal Detachment
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal Haemorrhage
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal Vein Occlusion
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Vitreous Haemorrhage
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Ear and labyrinth disorders
    Meniere's Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Otosclerosis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 83 (0.00%)
    3 / 82 (3.66%)
    1 / 159 (0.63%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Abdominal Hernia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Abdominal Pain
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Constipation
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Diarrhoea
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         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
    Haemorrhoidal Haemorrhage
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Impaired Gastric Emptying
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal Hernia
         subjects affected / exposed
    2 / 83 (2.41%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Intestinal Prolapse
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Intra-Abdominal Haematoma
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesenteric Artery Thrombosis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Nausea
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    3 / 148 (2.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic Cyst
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Rectal Prolapse
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Umbilical Hernia
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    4 / 159 (2.52%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    9 / 148 (6.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis Acute
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Cholelithiasis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Drug-Induced Liver Injury
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Hepatic Mass
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Bladder Irritation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Diabetic Nephropathy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    End Stage Renal Disease
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Incontinence
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Renal Colic
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Renal Failure
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    3 / 159 (1.89%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal Impairment
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Urinary Bladder Polyp
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Urinary Incontinence
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Decubitus Ulcer
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Dermatitis
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Diabetic Foot
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Eczema
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Hidradenitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         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
    Skin Erosion
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin Lesion
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Skin Ulcer
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Back Pain
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Bursitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Diastasis Recti Abdominis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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 Deformity
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Intervertebral Disc Disorder
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Intervertebral Disc Protrusion
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Lumbar Spinal Stenosis
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 82 (2.44%)
    0 / 159 (0.00%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal Pain
         subjects affected / exposed
    1 / 83 (1.20%)
    2 / 82 (2.44%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis Of Jaw
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Pain In Extremity
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Periarthritis
         subjects affected / exposed
    2 / 83 (2.41%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid Arthritis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Spinal Osteoarthritis
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Spondylolisthesis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Synovial Cyst
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Synovitis
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Tendon Disorder
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Tenosynovitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    2 / 159 (1.26%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigger Finger
         subjects affected / exposed
    3 / 83 (3.61%)
    2 / 82 (2.44%)
    5 / 159 (3.14%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid Mass
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Metabolism and nutrition disorders
    Acetonaemia
         subjects affected / exposed
    6 / 83 (7.23%)
    9 / 82 (10.98%)
    9 / 159 (5.66%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    5 / 8
    8 / 10
    9 / 11
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Diabetes Mellitus Inadequate Control
         subjects affected / exposed
    5 / 83 (6.02%)
    7 / 82 (8.54%)
    10 / 159 (6.29%)
    18 / 148 (12.16%)
         occurrences causally related to treatment / all
    4 / 7
    4 / 7
    3 / 13
    18 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic Ketoacidosis
         subjects affected / exposed
    1 / 83 (1.20%)
    1 / 82 (1.22%)
    6 / 159 (3.77%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    6 / 7
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic Ketosis
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Hyperglycaemia
         subjects affected / exposed
    9 / 83 (10.84%)
    11 / 82 (13.41%)
    19 / 159 (11.95%)
    20 / 148 (13.51%)
         occurrences causally related to treatment / all
    6 / 10
    10 / 11
    19 / 26
    24 / 30
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    13 / 83 (15.66%)
    3 / 82 (3.66%)
    9 / 159 (5.66%)
    18 / 148 (12.16%)
         occurrences causally related to treatment / all
    3 / 13
    1 / 3
    7 / 16
    6 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ketosis
         subjects affected / exposed
    1 / 83 (1.20%)
    3 / 82 (3.66%)
    4 / 159 (2.52%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 5
    3 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Overweight
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Weight Fluctuation
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Infections and infestations
    Abdominal Wall Abscess
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Anal Abscess
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Appendicitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         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
    Bronchitis
         subjects affected / exposed
    2 / 83 (2.41%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter Site Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Cellulitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Cystitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device Related Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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 Foot Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Endocarditis Staphylococcal
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Gastroenteritis
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    5 / 148 (3.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Norovirus
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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 Viral
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Herpes Zoster
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected Skin Ulcer
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Localised Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Lung Abscess
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    0 / 148 (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
    Medical Device Site Infection
         subjects affected / exposed
    12 / 83 (14.46%)
    5 / 82 (6.10%)
    5 / 159 (3.14%)
    11 / 148 (7.43%)
         occurrences causally related to treatment / all
    8 / 12
    2 / 5
    3 / 5
    9 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    1 / 159 (0.63%)
    0 / 148 (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
    Pharyngitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Pneumonia
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Pyelitis
         subjects affected / exposed
    1 / 83 (1.20%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    0 / 148 (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
    Pyelonephritis
         subjects affected / exposed
    0 / 83 (0.00%)
    2 / 82 (2.44%)
    2 / 159 (1.26%)
    1 / 148 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Sepsis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Sinusitis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    1 / 159 (0.63%)
    0 / 148 (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
    Urinary Tract Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    1 / 82 (1.22%)
    3 / 159 (1.89%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    2 / 148 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    0 / 159 (0.00%)
    1 / 148 (0.68%)
         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
    Insuman comparative phase Insuplant comparative phase Insuplant phase Insuman phase
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    74 / 83 (89.16%)
    66 / 82 (80.49%)
    130 / 159 (81.76%)
    101 / 148 (68.24%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 83 (4.82%)
    5 / 82 (6.10%)
    4 / 159 (2.52%)
    9 / 148 (6.08%)
         occurrences all number
    4
    5
    4
    9
    Lymphocele
         subjects affected / exposed
    0 / 83 (0.00%)
    3 / 82 (3.66%)
    8 / 159 (5.03%)
    6 / 148 (4.05%)
         occurrences all number
    0
    3
    8
    7
    Surgical and medical procedures
    Cataract Operation
         subjects affected / exposed
    2 / 83 (2.41%)
    7 / 82 (8.54%)
    1 / 159 (0.63%)
    1 / 148 (0.68%)
         occurrences all number
    3
    7
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 83 (1.20%)
    4 / 82 (4.88%)
    11 / 159 (6.92%)
    7 / 148 (4.73%)
         occurrences all number
    1
    4
    12
    10
    Oropharyngeal Pain
         subjects affected / exposed
    4 / 83 (4.82%)
    1 / 82 (1.22%)
    8 / 159 (5.03%)
    2 / 148 (1.35%)
         occurrences all number
    4
    1
    16
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 83 (7.23%)
    8 / 82 (9.76%)
    10 / 159 (6.29%)
    9 / 148 (6.08%)
         occurrences all number
    7
    11
    15
    11
    Eye disorders
    Macular Oedema
         subjects affected / exposed
    5 / 83 (6.02%)
    3 / 82 (3.66%)
    3 / 159 (1.89%)
    1 / 148 (0.68%)
         occurrences all number
    5
    5
    3
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 83 (0.00%)
    0 / 82 (0.00%)
    4 / 159 (2.52%)
    8 / 148 (5.41%)
         occurrences all number
    0
    0
    4
    8
    Influenza Like Illness
         subjects affected / exposed
    4 / 83 (4.82%)
    1 / 82 (1.22%)
    5 / 159 (3.14%)
    11 / 148 (7.43%)
         occurrences all number
    4
    1
    5
    14
    Medical Device Site Pain
         subjects affected / exposed
    1 / 83 (1.20%)
    2 / 82 (2.44%)
    7 / 159 (4.40%)
    14 / 148 (9.46%)
         occurrences all number
    1
    2
    7
    14
    Oedema Peripheral
         subjects affected / exposed
    0 / 83 (0.00%)
    5 / 82 (6.10%)
    3 / 159 (1.89%)
    5 / 148 (3.38%)
         occurrences all number
    0
    7
    4
    5
    Pyrexia
         subjects affected / exposed
    3 / 83 (3.61%)
    0 / 82 (0.00%)
    3 / 159 (1.89%)
    8 / 148 (5.41%)
         occurrences all number
    3
    0
    3
    9
    Psychiatric disorders
    Depression
         subjects affected / exposed
    10 / 83 (12.05%)
    2 / 82 (2.44%)
    7 / 159 (4.40%)
    2 / 148 (1.35%)
         occurrences all number
    10
    2
    7
    2
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    5 / 83 (6.02%)
    3 / 82 (3.66%)
    14 / 159 (8.81%)
    16 / 148 (10.81%)
         occurrences all number
    6
    3
    17
    18
    Diarrhoea
         subjects affected / exposed
    3 / 83 (3.61%)
    3 / 82 (3.66%)
    8 / 159 (5.03%)
    12 / 148 (8.11%)
         occurrences all number
    4
    4
    8
    12
    Gastrointestinal Disorder
         subjects affected / exposed
    4 / 83 (4.82%)
    1 / 82 (1.22%)
    8 / 159 (5.03%)
    0 / 148 (0.00%)
         occurrences all number
    5
    1
    8
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 83 (13.25%)
    4 / 82 (4.88%)
    8 / 159 (5.03%)
    5 / 148 (3.38%)
         occurrences all number
    11
    4
    10
    5
    Back Pain
         subjects affected / exposed
    12 / 83 (14.46%)
    7 / 82 (8.54%)
    8 / 159 (5.03%)
    9 / 148 (6.08%)
         occurrences all number
    19
    8
    11
    9
    Musculoskeletal Pain
         subjects affected / exposed
    5 / 83 (6.02%)
    3 / 82 (3.66%)
    8 / 159 (5.03%)
    4 / 148 (2.70%)
         occurrences all number
    5
    3
    9
    5
    Pain In Extremity
         subjects affected / exposed
    6 / 83 (7.23%)
    3 / 82 (3.66%)
    11 / 159 (6.92%)
    7 / 148 (4.73%)
         occurrences all number
    6
    3
    12
    8
    Tendonitis
         subjects affected / exposed
    8 / 83 (9.64%)
    6 / 82 (7.32%)
    9 / 159 (5.66%)
    5 / 148 (3.38%)
         occurrences all number
    8
    6
    10
    5
    Metabolism and nutrition disorders
    Acetonaemia
         subjects affected / exposed
    7 / 83 (8.43%)
    10 / 82 (12.20%)
    8 / 159 (5.03%)
    4 / 148 (2.70%)
         occurrences all number
    9
    14
    9
    4
    Diabetes Mellitus Inadequate Control
         subjects affected / exposed
    12 / 83 (14.46%)
    13 / 82 (15.85%)
    24 / 159 (15.09%)
    15 / 148 (10.14%)
         occurrences all number
    12
    18
    28
    15
    Hyperglycaemia
         subjects affected / exposed
    18 / 83 (21.69%)
    8 / 82 (9.76%)
    30 / 159 (18.87%)
    15 / 148 (10.14%)
         occurrences all number
    21
    10
    34
    15
    Ketosis
         subjects affected / exposed
    6 / 83 (7.23%)
    0 / 82 (0.00%)
    6 / 159 (3.77%)
    2 / 148 (1.35%)
         occurrences all number
    8
    0
    7
    2
    Vitamin D Deficiency
         subjects affected / exposed
    2 / 83 (2.41%)
    7 / 82 (8.54%)
    5 / 159 (3.14%)
    4 / 148 (2.70%)
         occurrences all number
    2
    7
    5
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    24 / 83 (28.92%)
    20 / 82 (24.39%)
    27 / 159 (16.98%)
    13 / 148 (8.78%)
         occurrences all number
    36
    35
    38
    15
    Cystitis
         subjects affected / exposed
    4 / 83 (4.82%)
    2 / 82 (2.44%)
    14 / 159 (8.81%)
    9 / 148 (6.08%)
         occurrences all number
    5
    5
    15
    13
    Ear Infection
         subjects affected / exposed
    5 / 83 (6.02%)
    3 / 82 (3.66%)
    7 / 159 (4.40%)
    3 / 148 (2.03%)
         occurrences all number
    5
    3
    9
    3
    Gastroenteritis
         subjects affected / exposed
    10 / 83 (12.05%)
    9 / 82 (10.98%)
    15 / 159 (9.43%)
    10 / 148 (6.76%)
         occurrences all number
    11
    9
    20
    12
    Influenza
         subjects affected / exposed
    10 / 83 (12.05%)
    9 / 82 (10.98%)
    25 / 159 (15.72%)
    20 / 148 (13.51%)
         occurrences all number
    10
    11
    32
    28
    Nasopharyngitis
         subjects affected / exposed
    12 / 83 (14.46%)
    9 / 82 (10.98%)
    16 / 159 (10.06%)
    19 / 148 (12.84%)
         occurrences all number
    16
    9
    17
    26
    Pharyngitis
         subjects affected / exposed
    5 / 83 (6.02%)
    3 / 82 (3.66%)
    2 / 159 (1.26%)
    2 / 148 (1.35%)
         occurrences all number
    6
    3
    3
    2
    Pneumonia
         subjects affected / exposed
    2 / 83 (2.41%)
    1 / 82 (1.22%)
    2 / 159 (1.26%)
    8 / 148 (5.41%)
         occurrences all number
    2
    1
    2
    9
    Rhinitis
         subjects affected / exposed
    6 / 83 (7.23%)
    3 / 82 (3.66%)
    10 / 159 (6.29%)
    1 / 148 (0.68%)
         occurrences all number
    7
    4
    14
    1
    Sinusitis
         subjects affected / exposed
    8 / 83 (9.64%)
    7 / 82 (8.54%)
    7 / 159 (4.40%)
    6 / 148 (4.05%)
         occurrences all number
    10
    7
    7
    6
    Tonsillitis
         subjects affected / exposed
    6 / 83 (7.23%)
    5 / 82 (6.10%)
    5 / 159 (3.14%)
    0 / 148 (0.00%)
         occurrences all number
    8
    5
    5
    0
    Tooth Abscess
         subjects affected / exposed
    6 / 83 (7.23%)
    2 / 82 (2.44%)
    6 / 159 (3.77%)
    3 / 148 (2.03%)
         occurrences all number
    6
    3
    7
    5
    Tooth Infection
         subjects affected / exposed
    4 / 83 (4.82%)
    3 / 82 (3.66%)
    10 / 159 (6.29%)
    5 / 148 (3.38%)
         occurrences all number
    5
    4
    12
    6
    Tracheitis
         subjects affected / exposed
    7 / 83 (8.43%)
    0 / 82 (0.00%)
    5 / 159 (3.14%)
    1 / 148 (0.68%)
         occurrences all number
    9
    0
    6
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 83 (0.00%)
    3 / 82 (3.66%)
    8 / 159 (5.03%)
    1 / 148 (0.68%)
         occurrences all number
    0
    3
    8
    1
    Urinary Tract Infection
         subjects affected / exposed
    14 / 83 (16.87%)
    8 / 82 (9.76%)
    18 / 159 (11.32%)
    15 / 148 (10.14%)
         occurrences all number
    25
    16
    29
    21

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Mar 2011
    Following amendments were made: - To comply with the standard practice in the real life for the Insuplant non comparative phase: time to refill and blood withdrawal for HbA1c and anti-insulin antibodies were scheduled according to the site usual care. - Inclusion criteria for Insuman non comparative phase were added. Subjets who didn’t participate to the comparative phase nor to the Insuplant non-comparative phase were allowed to participate directly to the Insuman non-comparative phase. - Correction of a mistake in the initial version of the protocol: no blood sample was collected for fasting plasma glucose, lipid profile (total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides) and chemistry (aspartate transferase, alanine transaminase, serum creatinine).
    06 Jun 2011
    - To allow the inclusion, in the Insuman non-comparative phase, of subjects not previously treated with Minimed implantable pump, but requiring CIPII therapy. - To allow subjects being pregnant during Insuman non-comparative phase to continue their treatment with Insuman Implantable 400 IU/mL as the duration of this phase was planned to end only when the product was marketed and as the safety profile of insulin is well established in pregnancy.

    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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