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    Clinical Trial Results:
    Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.

    Summary
    EudraCT number
    2005-002759-42
    Trial protocol
    DE  
    Global end of trial date
    28 Sep 2007

    Results information
    Results version number
    v1(current)
    This version publication date
    23 May 2016
    First version publication date
    12 Jun 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AGLU02704
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00158600
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Genzyme Corporation
    Sponsor organisation address
    500 Kendall Street, Cambridge, MA, United States, 02142
    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 Nov 2007
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Sep 2007
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the study are: 1) to evaluate the safety profile of Myozyme; 2) to determine the effect of Myozyme treatment on functional endurance as measured by the Six Minute Walk Test (6MWT) 3) to determine the effect of Myozyme treatment on respiratory muscle weakness as measured by Forced Vital Capacity (FVC) in the upright position ; and 4) to determine in a subset of subjects the PK profile of Myozyme in subjects with late-onset Pompe disease. The study wil be considered to have met its primary efficacy objective if a statistically significant treatment effect of Myozyme over placebo is demonstrated in the 6 MWT distance walked.
    Protection of trial subjects
    Pediatric subjects: The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort. Adult 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
    06 Sep 2005
    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
    France: 10
    Country: Number of subjects enrolled
    United States: 58
    Country: Number of subjects enrolled
    Netherlands: 22
    Worldwide total number of subjects
    90
    EEA total number of subjects
    32
    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)
    1
    Adolescents (12-17 years)
    3
    Adults (18-64 years)
    81
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    One hundred subjects screened and 90 enrolled.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Alglucosidase Alfa
    Arm description
    Alglucosidase alfa for 78 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Alglucosidase Alfa
    Investigational medicinal product code
    Other name
    Myozyme, Lumizyme
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow).

    Arm title
    Placebo
    Arm description
    Placebo for 78 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo matched to alglucosidase alfa every other week (qow).

    Number of subjects in period 1
    Alglucosidase Alfa Placebo
    Started
    60
    30
    Completed
    55
    26
    Not completed
    5
    4
         unable to commit time to study
    -
    1
         Death
    1
    -
         Withdrawal by Subject
    2
    2
         Adverse Event
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Alglucosidase Alfa
    Reporting group description
    Alglucosidase alfa for 78 weeks.

    Reporting group title
    Placebo
    Reporting group description
    Placebo for 78 weeks.

    Reporting group values
    Alglucosidase Alfa Placebo Total
    Number of subjects
    60 30 90
    Age categorical
    Units: Subjects
    Age continuous
    Age at First Infusion
    Units: years
        arithmetic mean (standard deviation)
    45.3 ± 12.37 42.6 ± 11.63 -
    Gender categorical
    Units: Subjects
        Female
    26 19 45
        Male
    34 11 45
    Race/Ethnicity
    Units: Subjects
        Hispanic
    1 1 2
        Asian
    1 1 2
        Black or African American
    0 0 0
        White
    57 27 84
        Unknown or not reported
    1 1 2

    End points

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    End points reporting groups
    Reporting group title
    Alglucosidase Alfa
    Reporting group description
    Alglucosidase alfa for 78 weeks.

    Reporting group title
    Placebo
    Reporting group description
    Placebo for 78 weeks.

    Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events

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    End point title
    Summary of Subjects Reporting Treatment-Emergent Adverse Events [1]
    End point description
    Overall safety summary of subjects experiencing Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on Treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment, i.e., alglucosidase alfa or placebo. All subjects who received any amount of study treatment comprise the safety population. Subjects were considered, for safety analysis, to be in the treatment group of the treatment they actually received. Missing or invalid safety or resource utilization data were not replaced.
    End point type
    Primary
    End point timeframe
    weeks 0-78
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Since analysis is descriptive in nature, statistical data could not be provided. 
    End point values
    Alglucosidase Alfa Placebo
    Number of subjects analysed
    60
    30
    Units: subjects
        Subjects with Any AEs
    60
    30
        Subjects with Treatment-Related AEs
    32
    17
        Subjects with Infusion-Associated Reactions
    17
    7
        Subjects with SAEs
    13
    6
        Subjects with Severe AEs
    14
    10
        Subjects who Discontinued Due to AEs (incl death)
    3
    1
        Subjects who Died
    1
    0
    No statistical analyses for this end point

    Primary: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

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    End point title
    Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
    End point description
    Mean distance walked gives an indication of functional endurance. The greater the distance, the greater the endurance. Mean values of distance walked in a six-minute walk test are offered for baseline, week 78 (or last available observation), and the mean change from baseline (at week 78 or last available post-baseline observation). Intent-to-Treat (ITT) population. Last observation carried forward. The last available distance walked for one subject was the Baseline visit; therefore, this subject was excluded from the change from baseline calculation.
    End point type
    Primary
    End point timeframe
    weeks 0, 78
    End point values
    Alglucosidase Alfa Placebo
    Number of subjects analysed
    60
    30
    Units: meters
    arithmetic mean (standard deviation)
        Distance Walked at Baseline
    332.2 ± 126.69
    317.93 ± 132.29
        Distance Walked at Last Available Observation
    357.85 ± 141.32
    313.07 ± 144.69
        Change at Last Available Observation from Baseline
    26.08 ± 64.41
    -4.87 ± 45.24
    Statistical analysis title
    Alglucosidase Alfa vs Placebo
    Statistical analysis description
    The difference between alglucosidase alfa and placebo treatment groups in change in distance walked from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
    Comparison groups
    Alglucosidase Alfa v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0347 [2]
    Method
    ANCOVA
    Parameter type
    Difference
    Point estimate
    28.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.07
         upper limit
    54.17
    Notes
    [2] - The threshold for determining statistical significance was 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.

    Primary: Percent of Predicted Forced Vital Capacity (FVC)

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    End point title
    Percent of Predicted Forced Vital Capacity (FVC)
    End point description
    Forced vital capacity is a standard pulmonary function test used to quantify respiratory muscle weakness. Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. ITT population. Last observation carried forward.
    End point type
    Primary
    End point timeframe
    weeks 0, 78
    End point values
    Alglucosidase Alfa Placebo
    Number of subjects analysed
    60
    30
    Units: percent predicted FVC
    arithmetic mean (standard deviation)
        Baseline (week 0)
    55.43 ± 14.44
    53 ± 15.66
        Week 78 (or last observation)
    56.71 ± 16.3
    50.7 ± 14.88
        Change at Week 78 from Baseline
    1.25 ± 5.55
    -2.3 ± 4.33
    Statistical analysis title
    Alglucosidase Alfa vs Placebo
    Statistical analysis description
    The difference between alglucosidase alfa and placebo treatment groups in change in % predicted FVC from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
    Comparison groups
    Alglucosidase Alfa v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0055 [3]
    Method
    ANCOVA
    Parameter type
    Difference
    Point estimate
    3.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.03
         upper limit
    5.77
    Notes
    [3] - The threshold for determining statistical significance is 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.

    Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)

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    End point title
    Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC) [4] [5]
    End point description
    Area under the plasma concentration versus time curve from time zero (pre-dose) to 16 hours after the end of infusion. Blood sample time points were 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes. The subgroup of subjects for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.
    End point type
    Primary
    End point timeframe
    weeks 0, 12 and 52
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data are reported for pharmacokinetic analysis.
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetic data were measured only for alglucosidase alfa, hence data were provided for this arm only.
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    32
    Units: ug*h/mL
    arithmetic mean (standard deviation)
        Week 0
    2672.47 ± 1139.85
        Week 12
    2386.76 ± 555.09
        Week 52
    2699.28 ± 999.97
        Pooled
    2586.17 ± 933.28
    No statistical analyses for this end point

    Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)

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    End point title
    Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax) [6] [7]
    End point description
    Maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes. The subgroup of subjects for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.
    End point type
    Primary
    End point timeframe
    weeks 0, 12, 52
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data are reported for pharmacokinetic analysis.
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetic data were measured only for alglucosidase alfa, hence data were provided for this arm only.
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    32
    Units: ng/mL
    arithmetic mean (standard deviation)
        Week 0
    385237 ± 105585
        Week 12
    349269 ± 78620
        Week 52
    369744 ± 88203
        Pooled
    368083 ± 91721
    No statistical analyses for this end point

    Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)

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    End point title
    Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax) [8] [9]
    End point description
    Time to maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes. The subgroup of subjects for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.
    End point type
    Primary
    End point timeframe
    weeks 0, 12, 52
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data are reported for pharmacokinetic analysis.
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetic data were measured only for alglucosidase alfa, hence data were provided for this arm only.
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    32
    Units: hours
    arithmetic mean (standard deviation)
        Week 0
    3.62 ± 0.33
        Week 12
    3.62 ± 0.28
        Week 52
    3.64 ± 0.31
        Pooled
    3.63 ± 0.3
    No statistical analyses for this end point

    Secondary: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

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    End point title
    Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)
    End point description
    Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and is an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) * 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength. ITT population. Last observation carried forward.
    End point type
    Secondary
    End point timeframe
    weeks 0, 78
    End point values
    Alglucosidase Alfa Placebo
    Number of subjects analysed
    60
    30
    Units: percent predicted QMT
    arithmetic mean (standard deviation)
        Baseline (week 0)
    37.69 ± 18.88
    32.49 ± 18.24
        Week 78 (or last available observation)
    39.05 ± 21.83
    30.4 ± 20.54
        Change at Week 78 from Baseline
    1.22 ± 9.88
    -2.08 ± 5.11
    Statistical analysis title
    Alglucosidase Alfa vs Placebo
    Statistical analysis description
    The difference between alglucosidase alfa and placebo treatment groups in change in QMT from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
    Comparison groups
    Alglucosidase Alfa v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1093 [10]
    Method
    ANCOVA
    Parameter type
    Difference
    Point estimate
    3.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.73
         upper limit
    7.08
    Notes
    [10] - The threshold for determining statistical significance is 0.05. No adjustment for multiple comparison was made for secondary efficacy endpoints.

    Secondary: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

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    End point title
    Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey
    End point description
    The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Scores (PCS) report the four domains of physical functioning, role-physical, bodily pain, and general health. Higher scores are associated with better quality of life. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. The PCS scores are reported. ITT population. Last observation carried forward.
    End point type
    Secondary
    End point timeframe
    weeks 0, 78
    End point values
    Alglucosidase Alfa Placebo
    Number of subjects analysed
    60
    30
    Units: Units on a scale
    arithmetic mean (standard deviation)
        PCS at Baseline (week 0)
    34.33 ± 8.93
    34.91 ± 7.26
        PCS at Week 78 (or last available observation)
    35.11 ± 9.84
    36.47 ± 9.57
    Statistical analysis title
    Alglucosidase Alfa vs Placebo
    Statistical analysis description
    The difference between alglucosidase alfa and placebo treatment groups in change in PCS from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
    Comparison groups
    Alglucosidase Alfa v Placebo
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8333 [11]
    Method
    ANCOVA
    Parameter type
    Difference
    Point estimate
    -0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.83
         upper limit
    3.09
    Notes
    [11] - The threshold for determining statistical significance is 0.05. No adjustment for multiple comparison was made for secondary efficacy endpoints.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All Adverse Events (AE) were collected following the initiation of treatment (ie alglucosidase alfa or placebo) up to the end of study (0 - 78 weeks) regardless of seriousness or relationship to investigational product
    Adverse event reporting additional description
    Reported AEs and deaths are treatment-emergent that is AEs and deaths that occurred following the initiation of study treatment i.e. alglucosidase alfa or placebo.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    9.1
    Reporting groups
    Reporting group title
    Alglucosidase Alfa
    Reporting group description
    Alglucosidase alfa for 78 weeks.

    Reporting group title
    Placebo
    Reporting group description
    Placebo for 78 weeks.

    Serious adverse events
    Alglucosidase Alfa Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 60 (21.67%)
    6 / 30 (20.00%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary Artery Disease
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular Tachycardia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Lung Disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Throat Tightness
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Brain Stem Ischaemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Headache
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest Discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioneurotic Oedema
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septal Panniculitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Flank Pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral Disc Protrusion
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Alglucosidase Alfa Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    60 / 60 (100.00%)
    30 / 30 (100.00%)
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Diastolic Hypotension
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Flushing
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 30 (6.67%)
         occurrences all number
    5
    2
    Haematoma
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Hot Flush
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Hypertension
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    3
    1
    Hypotension
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Phlebitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Raynaud's Phenomenon
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Vasoconstriction
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic Naevus
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    24
    0
    General disorders and administration site conditions
    Application Site Vesicles
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Asthenia
         subjects affected / exposed
    3 / 60 (5.00%)
    4 / 30 (13.33%)
         occurrences all number
    3
    8
    Axillary Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Catheter Related Complication
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Catheter Site Pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    7
    0
    Catheter Site Related Reaction
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Chest Discomfort
         subjects affected / exposed
    6 / 60 (10.00%)
    1 / 30 (3.33%)
         occurrences all number
    15
    1
    Chest Pain
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Chills
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    3
    4
    Fatigue
         subjects affected / exposed
    7 / 60 (11.67%)
    6 / 30 (20.00%)
         occurrences all number
    9
    14
    Feeling Abnormal
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Feeling Cold
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Feeling Hot
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 30 (6.67%)
         occurrences all number
    4
    3
    Feeling Hot And Cold
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Gait Disturbance
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Hangover
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Influenza Like Illness
         subjects affected / exposed
    2 / 60 (3.33%)
    4 / 30 (13.33%)
         occurrences all number
    2
    5
    Infusion Site Bruising
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Infusion Site Pain
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Infusion Site Paraesthesia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Infusion Site Reaction
         subjects affected / exposed
    5 / 60 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    6
    0
    Injection Site Phlebitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Local Swelling
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    14
    2
    Malaise
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Oedema Peripheral
         subjects affected / exposed
    10 / 60 (16.67%)
    3 / 30 (10.00%)
         occurrences all number
    12
    5
    Pain
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    8
    1
    Pitting Oedema
         subjects affected / exposed
    2 / 60 (3.33%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Puncture Site Haemorrhage
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Thirst
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    8 / 60 (13.33%)
    8 / 30 (26.67%)
         occurrences all number
    8
    11
    Vessel Puncture Site Haematoma
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    4
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 60 (3.33%)
    3 / 30 (10.00%)
         occurrences all number
    4
    3
    Abnormal Dreams
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Depression
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    3
    2
    Insomnia
         subjects affected / exposed
    6 / 60 (10.00%)
    2 / 30 (6.67%)
         occurrences all number
    7
    2
    Panic Attack
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Stress
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    9
    0
    Reproductive system and breast disorders
    Breast Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Breast Swelling
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Breast Tenderness
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Fibrocystic Breast Disease
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Dysmenorrhoea
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    Genital Pruritus Female
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Menstrual Discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Menstruation Irregular
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Scrotal Cyst
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vaginal Haemorrhage
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Animal Bite
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Arthropod Bite
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Arthropod Sting
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Back Injury
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    4 / 60 (6.67%)
    6 / 30 (20.00%)
         occurrences all number
    6
    7
    Excoriation
         subjects affected / exposed
    0 / 60 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    4
    Fall
         subjects affected / exposed
    39 / 60 (65.00%)
    20 / 30 (66.67%)
         occurrences all number
    154
    120
    Femur Fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Foot Fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Humerus Fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Injury
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Injury Corneal
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Joint Dislocation
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Joint Sprain
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Laceration
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Ligament Injury
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Limb Crushing Injury
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Limb Injury
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Muscle Strain
         subjects affected / exposed
    4 / 60 (6.67%)
    4 / 30 (13.33%)
         occurrences all number
    5
    5
    Periorbital Haematoma
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Procedural Pain
         subjects affected / exposed
    9 / 60 (15.00%)
    3 / 30 (10.00%)
         occurrences all number
    11
    6
    Repetitive Strain Injury
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Rib Fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Road Traffic Accident
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Skeletal Injury
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Skin Laceration
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    5
    1
    Tendon Injury
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Thermal Burn
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Tooth Fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Traumatic Ulcer
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Wound
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Vaccination Complication
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Blood Creatine Phosphokinase Mb Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Blood Folate Decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Blood Parathyroid Hormone Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Blood Glucose Increased
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Blood Pressure Increased
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    3
    2
    Blood Thyroid Stimulating Hormone Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Blood Urine Present
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Blood Uric Acid Increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Carbon Dioxide Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Electrocardiogram Qt Corrected Interval Prolonged
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Eosinophil Count Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Forced Expiratory Volume Decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Glucose Urine Present
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Heart Rate Irregular
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    International Normalised Ratio Decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Lymph Node Palpable
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Neutrophil Count Increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Oxygen Saturation Decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Protein Total Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Protein Urine Present
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Specific Gravity Urine Decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Urine Ketone Body Present
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Vitamin D Decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Weight Decreased
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Weight Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    White Blood Cell Count Increased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    White Blood Cells Urine Positive
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Angina Pectoris
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Bundle Branch Block Left
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Bundle Branch Block Right
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Coronary Artery Disease
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Palpitations
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    9
    1
    Sinus Tachycardia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tricuspid Valve Incompetence
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Bronchospasm
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    6 / 60 (10.00%)
    5 / 30 (16.67%)
         occurrences all number
    6
    5
    Dyspnoea Exertional
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Dyspnoea
         subjects affected / exposed
    7 / 60 (11.67%)
    4 / 30 (13.33%)
         occurrences all number
    10
    6
    Epistaxis
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    8
    0
    Increased Bronchial Secretion
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    5
    Lung Disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Lung Infiltration
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Nasal Congestion
         subjects affected / exposed
    2 / 60 (3.33%)
    2 / 30 (6.67%)
         occurrences all number
    2
    3
    Pharyngolaryngeal Pain
         subjects affected / exposed
    12 / 60 (20.00%)
    5 / 30 (16.67%)
         occurrences all number
    19
    9
    Paranasal Sinus Hypersecretion
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Postnasal Drip
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Rales
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Respiratory Distress
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Respiratory Failure
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Respiratory Tract Congestion
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    2
    Sinus Congestion
         subjects affected / exposed
    2 / 60 (3.33%)
    3 / 30 (10.00%)
         occurrences all number
    2
    3
    Sleep Apnoea Syndrome
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Sneezing
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Throat Irritation
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Throat Tightness
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Lymphadenopathy
         subjects affected / exposed
    5 / 60 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    6
    0
    Macrocytosis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Normochromic Normocytic Anaemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Areflexia
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 30 (6.67%)
         occurrences all number
    4
    2
    Balance Disorder
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Burning Sensation
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Carpal Tunnel Syndrome
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Disturbance In Attention
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Dizziness Postural
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Dizziness
         subjects affected / exposed
    14 / 60 (23.33%)
    6 / 30 (20.00%)
         occurrences all number
    31
    14
    Dysgeusia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    17
    Facial Palsy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Head Discomfort
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    4
    Headache
         subjects affected / exposed
    24 / 60 (40.00%)
    15 / 30 (50.00%)
         occurrences all number
    91
    129
    Hyperreflexia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    2 / 60 (3.33%)
    2 / 30 (6.67%)
         occurrences all number
    2
    3
    Hyporeflexia
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Intercostal Neuralgia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Intracranial Hypotension
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Lethargy
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Loss Of Consciousness
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Migraine
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    5
    4
    Nerve Compression
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Paraesthesia
         subjects affected / exposed
    6 / 60 (10.00%)
    4 / 30 (13.33%)
         occurrences all number
    16
    10
    Poor Quality Sleep
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Sinus Headache
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Somnolence
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Syncope Vasovagal
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    2
    Tremor
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Eye disorders
    Altered Visual Depth Perception
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Asthenopia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Cataract
         subjects affected / exposed
    4 / 60 (6.67%)
    2 / 30 (6.67%)
         occurrences all number
    4
    2
    Diplopia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Dry Eye
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Eye Pruritus
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Eye Irritation
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Lacrimation Increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vision Blurred
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Photophobia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Visual Disturbance
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Vitreous Floaters
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Auricular Swelling
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Ear Congestion
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Ear Discomfort
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    23
    1
    Hypoacusis
         subjects affected / exposed
    20 / 60 (33.33%)
    7 / 30 (23.33%)
         occurrences all number
    22
    7
    Ear Pain
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    3
    4
    Presbyacusis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Tympanic Membrane Scarring
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Tympanic Membrane Disorder
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Vertigo
         subjects affected / exposed
    4 / 60 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    6
    0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    2 / 60 (3.33%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Abdominal Distension
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Abdominal Mass
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Abdominal Pain
         subjects affected / exposed
    4 / 60 (6.67%)
    3 / 30 (10.00%)
         occurrences all number
    4
    3
    Abdominal Pain Lower
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Abdominal Pain Upper
         subjects affected / exposed
    6 / 60 (10.00%)
    2 / 30 (6.67%)
         occurrences all number
    23
    3
    Constipation
         subjects affected / exposed
    6 / 60 (10.00%)
    0 / 30 (0.00%)
         occurrences all number
    8
    0
    Dental Caries
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    18 / 60 (30.00%)
    13 / 30 (43.33%)
         occurrences all number
    43
    20
    Diverticulum
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Dry Mouth
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    5 / 60 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    8
    0
    Dysphagia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Epigastric Discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Flatulence
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Food Poisoning
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal Disorder
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Glossodynia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Haematochezia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Hiatus Hernia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Inguinal Hernia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Lip Swelling
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Nausea
         subjects affected / exposed
    11 / 60 (18.33%)
    10 / 30 (33.33%)
         occurrences all number
    38
    49
    Oesophageal Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Oral Mucosal Blistering
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Oral Pruritus
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Paraesthesia Oral
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Retching
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Stomach Discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Swollen Tongue
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Toothache
         subjects affected / exposed
    1 / 60 (1.67%)
    4 / 30 (13.33%)
         occurrences all number
    1
    6
    Vomiting
         subjects affected / exposed
    13 / 60 (21.67%)
    3 / 30 (10.00%)
         occurrences all number
    16
    5
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Nephrolithiasis
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Leukocyturia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Pollakiuria
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    2
    Urinary Incontinence
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Pyuria
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Urine Flow Decreased
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Urine Odour Abnormal
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Blister
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    3
    Cold Sweat
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Decubitus Ulcer
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Dermatitis Contact
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Drug Eruption
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Ecchymosis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Erythema
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    5
    1
    Heat Rash
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    5 / 60 (8.33%)
    0 / 30 (0.00%)
         occurrences all number
    10
    0
    Ingrowing Nail
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Photosensitivity Reaction
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Pruritus
         subjects affected / exposed
    6 / 60 (10.00%)
    1 / 30 (3.33%)
         occurrences all number
    15
    1
    Rash
         subjects affected / exposed
    6 / 60 (10.00%)
    3 / 30 (10.00%)
         occurrences all number
    10
    5
    Rash Macular
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Rash Maculo-Papular
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Rash Papular
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Rash Pruritic
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    7
    3
    Skin Burning Sensation
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Skin Lesion
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Skin Nodule
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    21
    0
    Skin Odour Abnormal
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Skin Warm
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Subcutaneous Nodule
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Telangiectasia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    6 / 60 (10.00%)
    0 / 30 (0.00%)
         occurrences all number
    15
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    18 / 60 (30.00%)
    9 / 30 (30.00%)
         occurrences all number
    27
    21
    Back Pain
         subjects affected / exposed
    14 / 60 (23.33%)
    7 / 30 (23.33%)
         occurrences all number
    22
    15
    Bursitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Bone Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Buttock Pain
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Costochondritis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Exostosis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Flank Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Foot Deformity
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Groin Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Joint Range Of Motion Decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Joint Swelling
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Muscle Atrophy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Muscle Contracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Muscle Spasms
         subjects affected / exposed
    14 / 60 (23.33%)
    6 / 30 (20.00%)
         occurrences all number
    18
    7
    Muscle Tightness
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    2
    Muscle Twitching
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    7
    1
    Muscular Weakness
         subjects affected / exposed
    6 / 60 (10.00%)
    3 / 30 (10.00%)
         occurrences all number
    8
    4
    Musculoskeletal Chest Pain
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    6
    1
    Musculoskeletal Discomfort
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal Disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal Pain
         subjects affected / exposed
    8 / 60 (13.33%)
    2 / 30 (6.67%)
         occurrences all number
    14
    3
    Musculoskeletal Stiffness
         subjects affected / exposed
    8 / 60 (13.33%)
    1 / 30 (3.33%)
         occurrences all number
    11
    1
    Myalgia
         subjects affected / exposed
    12 / 60 (20.00%)
    5 / 30 (16.67%)
         occurrences all number
    40
    14
    Neck Pain
         subjects affected / exposed
    7 / 60 (11.67%)
    5 / 30 (16.67%)
         occurrences all number
    9
    11
    Nose Deformity
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Osteopenia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Osteoporosis
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Pain In Extremity
         subjects affected / exposed
    15 / 60 (25.00%)
    7 / 30 (23.33%)
         occurrences all number
    27
    25
    Plantar Fasciitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Scoliosis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    Sensation Of Heaviness
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    6
    1
    Temporomandibular Joint Syndrome
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tendon Pain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Tendonitis
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Tenosynovitis Stenosans
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Diabetes Mellitus Non-Insulin-Dependent
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Hypernatraemia
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Cellulitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Bronchopneumonia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Dermatophytosis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Cystitis
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    2
    Eye Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Folliculitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Fungal Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Fungal Skin Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 30 (3.33%)
         occurrences all number
    5
    1
    Gastroenteritis Viral
         subjects affected / exposed
    3 / 60 (5.00%)
    3 / 30 (10.00%)
         occurrences all number
    5
    3
    Gastrointestinal Infection
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Genital Infection
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Gingival Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Herpes Simplex
         subjects affected / exposed
    4 / 60 (6.67%)
    3 / 30 (10.00%)
         occurrences all number
    6
    4
    Herpes Virus Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    5 / 60 (8.33%)
    7 / 30 (23.33%)
         occurrences all number
    8
    8
    Kidney Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Laryngitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Localised Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    Mucosal Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    25 / 60 (41.67%)
    16 / 30 (53.33%)
         occurrences all number
    45
    25
    Otitis Media
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Postoperative Wound Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Rash Pustular
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Respiratory Tract Infection
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Rhinitis
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Sinusitis
         subjects affected / exposed
    4 / 60 (6.67%)
    4 / 30 (13.33%)
         occurrences all number
    5
    5
    Tinea Pedis
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Tonsillitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Tooth Infection
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    11 / 60 (18.33%)
    3 / 30 (10.00%)
         occurrences all number
    16
    3
    Urinary Tract Infection
         subjects affected / exposed
    5 / 60 (8.33%)
    4 / 30 (13.33%)
         occurrences all number
    6
    7
    Vaginal Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Viral Infection
         subjects affected / exposed
    2 / 60 (3.33%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Vulvovaginal Mycotic Infection
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    1
    Wound Infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Sep 2005
    - Subjects who transferred to regional investigational sites after 6 months of treatment could complete the remaining infusion visits at the transfer site. The Week 38 and Week 52 or early withdrawal infusions were no longer required to be done at the primary site. - Conduct of the 6MWT at Screening/Baseline was changed from 2 tests performed on the same day to testing on 2 consecutive days. - Inclusion criterion, which required the subject to have a forced expiratory volume in the first second of the FVC maneuver (FEV1)/FVC value of 70% predicted in the upright position, was deleted. The purpose of this criterion was to identify subjects with confounding obstructive disease that was NOT related to Pompe disease. However, weakness in the supporting respiratory muscles could prevent subjects from exhaling sufficient volume in the first second of the FVC maneuver (FEV1), causing what appears to be mild obstructive involvement in addition to the restrictive involvement caused by diaphragmatic weakness. - Exclusion for major congenital anomaly was limited to those that in the judgment of the Investigator would significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
    26 May 2006
    - The infusion rate schedule was adjusted to a maximum rate of approximately 7 mg/kg/hr to assist in Infusion-associated reaction (IAR) management, consistent with infantile-onset studies of Pompe disease conducted by Genzyme. In Protocol Amendment 3, this infusion rate schedule was subsequently designated as “recommended” to allow investigator discretion in setting the infusion rate.
    16 Aug 2006
    - The infusion rate schedule as adjusted in Amendment 2 was designated as “recommended” to allow investigator discretion in setting the infusion rate. -It proposed an adaptive, information-based design.

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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