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A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease

Sponsor
Genzyme, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00081497
Collaborator
(none)
67
Enrollment
25
Locations
1
Arm
20
Duration (Months)
2.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

People with Fabry Disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to break down and removes certain types of fatty substances called "glycolipids". These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid (globatriaosylceramide or GL-3) levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study analyzed the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease that previously participated in the AGAL-008-00 (NCT0074984) study.

Condition or Disease Intervention/Treatment Phase
  • Biological: agalsidase beta
 Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
67 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multi-Center, Open-Label Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease That Previously Participated in the AGAL-008-00 Study
Study Start Date :
Jan 1, 2004
Actual Primary Completion Date :
Sep 1, 2005
Actual Study Completion Date :
Sep 1, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Fabrazyme 1.0 mg/kg every 2 weeks

This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment.

Biological: agalsidase beta
1.0 mg/kg every 2 weeks
Other Names:
  • Fabrazyme
  • r-hαGAL

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Difference in Inverse Serum Creatinine Within Patients' Slopes Between the Placebo AGAL-008-00 (NCT00074984) and Fabrazyme AGAL02503 (NCT00081497) Periods [Placebo period AGAL-008-00 (up to 35 months) through Fabrazyme period AGAL02503 (18 months)]

      The primary efficacy analysis was the summary of change in slope of inverse serum creatinine for Placebo/Fabrazyme patients in the Intent to Treat (ITT) Population. It compared the placebo period slope with the Fabrazyme period slope.

    Secondary Outcome Measures

    1. Serum Creatinine at Pre-Fabrazyme and 6, 12, and 18 Months [Pre-Fabrazyme, 6, 12, and 18 months]

      Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).

    2. Estimated Glomerular Filtration Rate (eGFR) at Pre-Fabrazyme and 6, 12, and 18 Months [Pre-Fabrazyme, 6, 12, and 18 months]

      Pre-Fabrazyme=baseline visit of AGAL-00-800 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).

    3. Plasma Globotriaosylceramide (GL-3) (Normal Plasma GL-3 Level is ≤ 7.03 µg/mL) at Pre-Fabrazyme and 6, 12, and 18 Months [Pre-Fabrazyme and 6, 12, and 18 months]

      Pre-Fabrazyme=baseline visit of AGAL00800 for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL00800; assessment prior to first Fabrazyme infusion in AGAL02503 for placebo patients who did not transition to Fabrazyme in AGAL00800.

    4. Proteinuria at Pre-Fabrazyme and 6, 12, and 18 Months [Pre-Fabrazyme and 6, 12, and 18 months]

      Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients must have successfully completed the previous double-blind study AGAL-008-00 (NCT00074984)

    • Patients must provide written informed consent prior to study participation

    • Female patients of childbearing potential must have a negative pregnancy test prior to each dosing and all female patients must use a medically accepted form of contraception throughout the study

    Exclusion Criteria:

    • The patient was unable to complete AGAL-008-00 (NCT00074984)

    • The patient has undergone kidney transplantation or is currently on dialysis

    • The patient has diabetes mellitus or presence of confounding renal disease

    • The patient has a clinically significant organic disease or an unstable condition that precludes participation

    • The patient is unwilling to comply with the protocol requirements

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294-0006
    2 Cedars-Sinai Medical Center Los Angeles California United States 90048
    3 University of San Francisco San Francisco California United States 94143
    4 University of Connecticut Health Partners West Hartford Connecticut United States 06119
    5 Oncology Hematology Association Coral Springs Florida United States 33065
    6 Emory University School of Medicine Atlanta Georgia United States 30322
    7 Children's Memorial Hospital Chicago Illinois United States 60614
    8 University of Kansas Medical Center Kansas City Kansas United States 66160-7233
    9 Gene Therapy Center - Department of Pediatrics and Institute of Human Genetics Minneapolis Minnesota United States 55455
    10 Children's Hospital Buffalo New York United States 14209
    11 Mount Sinai School of Medicine New York New York United States 10029
    12 University of Rochester School of Medicine Rochester New York United States 14642
    13 Duke University Medical Center Durham North Carolina United States 27710
    14 Children's Hospital Medical Center Cincinnati Ohio United States 45229
    15 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    16 University of Pittsburgh Pittsburgh Pennsylvania United States 15261
    17 Baylor College of Medicine Houston Texas United States 77030
    18 University of Washington School of Medicine Seattle Washington United States 98195
    19 Queen Elizabeth II Health Center Halifax Nova Scotia Canada B3H 1V8
    20 North York General Hospital Toronto Ontario Canada M2K 1E1
    21 Hopital du Sacre-Coeur de Montreal Montreal Quebec Canada H4J 1C5
    22 University Hospital Prague Czech Republic
    23 Sopron Megyei Jogu Varos Erzsebet Korhaz Sopron Hungary 9400
    24 Klinika Chorob Metabolicznych Instytut Warsaw Poland 04-730
    25 Hope Hospital Manchester United Kingdom M6 8HD

    Sponsors and Collaborators

    • Genzyme, a Sanofi Company

    Investigators

    • Study Director: Medical Monitor, Genzyme, a Sanofi Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00081497
    Other Study ID Numbers:
    • AGAL02503
    First Posted:
    Apr 16, 2004
    Last Update Posted:
    Apr 2, 2015
    Last Verified:
    Mar 1, 2015
    Keywords provided by , ,
    alpha-galactosidase A
    a-GAL
    r-haGAL
    Fabry
    GL-3
    Fabrazyme
    Additional relevant MeSH terms:
    Fabry Disease

    Study Results

    Participant Flow

    Recruitment Details Only those patients who successfully completed the AGAL-008-00 (NCT00074984) trial were eligible for participation in the AGAL02503 (NCT00081497) extension study.
    Pre-assignment Detail
    Arm/Group Title Placebo/Fabrazyme Fabrazyme/Fabrazyme
    Arm/Group Description Patients who had been randomized to placebo during AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme (1.0 mg/kg every 2 weeks) prior to or at entry to AGAL02503 (NCT00081497). Patients who had been randomized to Fabrazyme in AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme (1.0 mg/kg every 2 weeks) prior to or at entry into AGAL02503 (NCT00081497).
    Period Title: Overall Study
    STARTED 28 39
    COMPLETED 25 37
    NOT COMPLETED 3 2

    Baseline Characteristics

    Arm/Group Title Placebo/Fabrazyme Fabrazyme/Fabrazyme Total
    Arm/Group Description Patients who had been randomized to placebo during AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme (1.0 mg/kg every 2 weeks) prior to or at entry to AGAL02503 (NCT00081497). Patients who had been randomized to Fabrazyme in AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme (1.0 mg/kg every 2 weeks) prior to or at entry into AGAL02503 (NCT00081497). Total of all reporting groups
    Overall Participants 28 39 67
    Age, Customized (participants) [Number]
    <40 years
    8
    28.6%
    7
    17.9%
    15
    22.4%
    ≥40 years
    20
    71.4%
    32
    82.1%
    52
    77.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    43.5
    (9.31)
    46.6
    (9.72)
    45.3
    (9.60)
    Sex: Female, Male (Count of Participants)
    Female
    4
    14.3%
    5
    12.8%
    9
    13.4%
    Male
    24
    85.7%
    34
    87.2%
    58
    86.6%
    Race/Ethnicity (participants) [Number]
    Caucasian
    24
    85.7%
    35
    89.7%
    59
    88.1%
    Black
    0
    0%
    0
    0%
    0
    0%
    Hispanic
    2
    7.1%
    3
    7.7%
    5
    7.5%
    Asian
    1
    3.6%
    1
    2.6%
    2
    3%
    Other
    1
    3.6%
    0
    0%
    1
    1.5%

    Outcome Measures

    1. Primary Outcome
    Title Difference in Inverse Serum Creatinine Within Patients' Slopes Between the Placebo AGAL-008-00 (NCT00074984) and Fabrazyme AGAL02503 (NCT00081497) Periods
    Description The primary efficacy analysis was the summary of change in slope of inverse serum creatinine for Placebo/Fabrazyme patients in the Intent to Treat (ITT) Population. It compared the placebo period slope with the Fabrazyme period slope.
    Time Frame Placebo period AGAL-008-00 (up to 35 months) through Fabrazyme period AGAL02503 (18 months)

    Outcome Measure Data

    Analysis Population Description
    ITT Population - Analysis compares results during the placebo period with those during the Fabrazyme period and includes only the 28 patients who were randomized to placebo in the AGAL-008-00 (NCT00074984) study; as such no formal sample size calculations were performed.
    Arm/Group Title Placebo Period - AGAL-008-00 (NCT00074984) Fabrazyme Period - AGAL02503 (NCT00081497)
    Arm/Group Description Patients who had been randomized to placebo during AGAL-008-00 (NCT00074984). Placebo patients who had been transitioned to open-label Fabrazyme prior to or at entry into AGAL02503 (NCT00081497). 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks for 18 months.
    Measure Participants 28 28
    Least Squares Mean (Standard Error) [dL/mg/year]
    -0.044
    (0.012)
    -0.073
    (0.011)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Period - AGAL-008-00 (NCT00074984), Fabrazyme Period - AGAL02503 (NCT00081497)
    Comments The statistical analysis represents the primary outcome measure results.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0130
    Comments
    Method Mixed Models Analysis
    Comments Mixed effects model with a population level (fixed effect) intercept and slope and a subject level (random effect) intercept and slope.
    Method of Estimation Estimation Parameter Change in Slope Mean
    Estimated Value -0.029
    Confidence Interval () 95%
    -0.051 to -0.007
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Post-Hoc Outcome
    Title Differences in Slopes of Estimated Glomerular Filtration Rate (eGFR) Comparing Randomized Placebo vs Fabrazyme Patients (Based on the Original Randomization in AGAL-008-00 (NCT00074984)) by Baseline eGFR Subgroups of >60 and ≤60 mL/Min/1.73 m^2.
    Description Summary of differences in slopes of eGFR comparing randomized placebo vs Fabrazyme patients by baseline eGFR subgroups. Differences in slopes are the placebo slope minus the Fabrazyme slope. Therefore, a negative difference indicates a greater decline in the placebo patients relative to the Fabrazyme patients.
    Time Frame Throughout study; 18 months

    Outcome Measure Data

    Analysis Population Description
    ITT population. For subgroup Estimated Glomerular Filtration Rate (eGFR) >60, there were 9 placebo patients and 15 Fabrazyme patients. For subgroup eGFR ≤60, there were 19 placebo patients and 24 Fabrazyme patients. For randomized Fabrazyme patients, both the double-blind and open-label data was used.
    Arm/Group Title Placebo - AGAL-008-00 (NCT00074984) eGFR >60 Fabrazyme - AGAL02503 (NCT00081497) eGFR >60 Placebo - AGAL-008-00 (NCT00074984) eGFR ≤60 Fabrazyme - AGAL02503 (NCT00081497) eGFR ≤60
    Arm/Group Description Patients who had been randomized to placebo during AGAL-008-00 (NCT00074984) using only placebo period data from the AGAL-008-00 (NCT00074984) study. Patients who had been randomized to Fabrazyme in AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme prior to or at entry into AGAL02503 (NCT00081497) using all Fabrazyme treatment period data from the AGAL00800 (NCT00074984) and AGAL02503 (NCT00081497) studies. Patients who had been randomized to placebo during AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme prior to or at entry to AGAL02503 (NCT00081497) using only placebo period data from the AGAL-008-00 (NCT00074984) study. Patients who had been randomized to Fabrazyme in AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme prior to or at entry into AGAL02503 (NCT00081497) using all Fabrazyme treatment period data from the AGAL00800 (NCT00074984) and AGAL02503 (NCT00081497) studies.
    Measure Participants 9 15 19 24
    Least Squares Mean (Standard Error) [mL/min/1.73m^2/year]
    -7.685
    (1.836)
    -0.898
    (1.129)
    -2.575
    (1.188)
    -4.906
    (0.900)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Period - AGAL-008-00 (NCT00074984), Fabrazyme Period - AGAL02503 (NCT00081497)
    Comments Statistical Analysis 1 represents the post-hoc outcome results for difference in slope mean of eGFR subgroup >60.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0027
    Comments
    Method Mixed Effects Model
    Comments
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value -6.787
    Confidence Interval () 95%
    -11.123 to -2.450
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo - AGAL-008-00 (NCT00074984) eGFR ≤60, Fabrazyme - AGAL02503 (NCT00081497) eGFR ≤60
    Comments Statistical Analysis 2 represents the post-hoc outcome results for difference in slope mean of eGFR subgroup ≤ 60.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1268
    Comments
    Method Mixed Effects Model
    Comments
    Method of Estimation Estimation Parameter Mean Difference
    Estimated Value 2.330
    Confidence Interval () 95%
    -0.685 to 5.345
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Serum Creatinine at Pre-Fabrazyme and 6, 12, and 18 Months
    Description Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).
    Time Frame Pre-Fabrazyme, 6, 12, and 18 months

    Outcome Measure Data

    Analysis Population Description
    ITT population-67 patients had assessments at 6 and 12 months while 65 patients had assessments at 18 months in the open-label extension study.
    Arm/Group Title Fabrazyme 1.0 mg/kg Every 2 Weeks
    Arm/Group Description 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks for 18 months. This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment.
    Measure Participants 67
    Serum Creatinine at Pre-Fabrazyme
    1.7
    (0.60)
    Serum Creatinine at 6 months post-treatment
    1.8
    (0.77)
    Serum Creatinine at 12 months post-treatment
    1.9
    (0.98)
    Serum Creatinine at 18 months post-treatment
    2.1
    (1.21)
    4. Secondary Outcome
    Title Estimated Glomerular Filtration Rate (eGFR) at Pre-Fabrazyme and 6, 12, and 18 Months
    Description Pre-Fabrazyme=baseline visit of AGAL-00-800 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).
    Time Frame Pre-Fabrazyme, 6, 12, and 18 months

    Outcome Measure Data

    Analysis Population Description
    ITT population-67 patients had assessments at 6 and 12 months while 65 patients had assessments at 18 months in the open-label extension study.
    Arm/Group Title Fabrazyme 1.0 mg/kg Every 2 Weeks
    Arm/Group Description 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks for 18 months. This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment.
    Measure Participants 67
    eGFR at Pre-Fabrazyme
    53.1
    (19.62)
    eGFR at 6 months post-treatment
    52.6
    (23.24)
    eGFR at 12 months post-treatment
    50.4
    (22.73)
    eGFR at 18 months post-treatment
    47.8
    (23.62)
    5. Secondary Outcome
    Title Plasma Globotriaosylceramide (GL-3) (Normal Plasma GL-3 Level is ≤ 7.03 µg/mL) at Pre-Fabrazyme and 6, 12, and 18 Months
    Description Pre-Fabrazyme=baseline visit of AGAL00800 for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL00800; assessment prior to first Fabrazyme infusion in AGAL02503 for placebo patients who did not transition to Fabrazyme in AGAL00800.
    Time Frame Pre-Fabrazyme and 6, 12, and 18 months

    Outcome Measure Data

    Analysis Population Description
    ITT population-64 patients had assessments at 6 and 18 months while 65 patients had assessments at 12 months in the open-label extension study.
    Arm/Group Title Fabrazyme 1.0 mg/kg Every 2 Weeks
    Arm/Group Description 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks for 18 months. This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment.
    Measure Participants 65
    Plasma GL-3 at Pre-Fabrazyme
    9.0
    (3.35)
    Plasma GL-3 at 6 months post-treatment
    4.8
    (1.76)
    Plasma GL-3 at 12 months post-treatment
    4.7
    (1.59)
    Plasma GL-3 at 18 months post-treatment
    4.6
    (1.82)
    6. Secondary Outcome
    Title Proteinuria at Pre-Fabrazyme and 6, 12, and 18 Months
    Description Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).
    Time Frame Pre-Fabrazyme and 6, 12, and 18 months

    Outcome Measure Data

    Analysis Population Description
    ITT population-62 patients had assessments at 6 months, 61 patients had assessments at 12 months, and 54 patients had assessments at 18 months in the open-label extension study.
    Arm/Group Title Fabrazyme 1.0 mg/kg Every 2 Weeks
    Arm/Group Description 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks for 18 months. This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment.
    Measure Participants 62
    Proteinuria at Pre-Fabrazyme
    1.3
    (1.46)
    Proteinuria at 6 months post-treatment
    1.1
    (1.19)
    Proteinuria at 12 months post-treatment
    1.3
    (1.77)
    Proteinuria at 18 months post-treatment
    1.3
    (1.55)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
    Arm/Group Title Fabrazyme/Fabrazyme Placebo/Fabrazyme Total
    Arm/Group Description Patients who had been randomized to Fabrazyme in AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme (1.0 mg/kg every 2 weeks) prior to or at entry into AGAL02503 (NCT00081497). Patients who had been randomized to placebo during AGAL-008-00 (NCT00074984) and were then transitioned to open-label Fabrazyme (1.0 mg/kg every 2 weeks) prior to or at entry to AGAL02503 (NCT00081497).
    All Cause Mortality
    Fabrazyme/Fabrazyme Placebo/Fabrazyme Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Fabrazyme/Fabrazyme Placebo/Fabrazyme Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/39 (48.7%) 12/28 (42.9%) 31/67 (46.3%)
    Cardiac disorders
    Acute myocardial infarction 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Angina pectoris 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Atrial fibrillation 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Atrioventricular block second degree 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Cardiac failure congestive 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Myocardial infarction 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Myocardial ischaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ventricular hypertrophy 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ventricular tachycardia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ear and labyrinth disorders
    Meniere's disease 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Gastrointestinal disorders
    Constipation 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Intestinal infarction 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Intestinal obstruction 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Large intestine perforation 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Nausea 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Peritonitis 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Vomiting 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    General disorders
    Chest pain 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Pyrexia 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Hepatobiliary disorders
    Cholelithiasis 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Immune system disorders
    Kidney transplant rejection 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Infections and infestations
    Cellulitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Lobar pneumonia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Localised infection 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Peritonitis bacterial 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Pneumonia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Sepsis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Streptococcal infection 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Viral infection 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Injury, poisoning and procedural complications
    Cardiac pacemaker malfunction 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Femoral neck fracture 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hand fracture 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Hip fracture 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Implantable defibrillator malfunction 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Joint dislocation 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Medical device complication 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Procedural hypertension 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Investigations
    Liver function test abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Skin test positive 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Metabolism and nutrition disorders
    Dehydration 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nervous system disorders
    Syncope 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Transient ischaemic attack 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Renal and urinary disorders
    Nephritis interstitial 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Renal failure 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Renal failure acute 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Renal failure chronic 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Renal impairment 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Reproductive system and breast disorders
    Uterine prolapse 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Mediastinal mass 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Pneumothorax 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Sleep apnoea syndrome 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Skin and subcutaneous tissue disorders
    Angioneurotic oedema 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Vascular disorders
    Hypertension 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Other (Not Including Serious) Adverse Events
    Fabrazyme/Fabrazyme Placebo/Fabrazyme Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 39/39 (100%) 27/28 (96.4%) 66/67 (98.5%)
    Blood and lymphatic system disorders
    Anaemia 5/39 (12.8%) 5/28 (17.9%) 10/67 (14.9%)
    Leukopenia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Lymphadenopathy 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Nephrogenic anaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Thrombocythaemia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Cardiac disorders
    Arrhythmia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Arrhythmia supraventricular 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Atrial fibrillation 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Atrial flutter 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Atrioventricular block first degree 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Bradycardia 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Bundle branch block left 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Bundle branch block right 4/39 (10.3%) 0/28 (0%) 4/67 (6%)
    Cardiac failure congestive 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Cardiomegaly 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dilatation atrial 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Dilatation ventricular 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Heart valve insufficiency 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Mitral valve incompetence 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Mitral valve prolapse 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Myocardial infarction 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Palpitations 4/39 (10.3%) 0/28 (0%) 4/67 (6%)
    Sinus bradycardia 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Supraventricular extrasystoles 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Tachyarrhythmia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Tachycardia 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Ventricular dysfunction 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ventricular extrasystoles 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Ventricular hypertrophy 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Ventricular tachycardia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Ventricular wall thickening 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Wolff-Parkinson-White syndrome 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Congenital, familial and genetic disorders
    Exomphalos 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Ear and labyrinth disorders
    Cerumen impaction 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Deafness 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Deafness neurosensory 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Ear canal erythema 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ear congestion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ear pain 6/39 (15.4%) 3/28 (10.7%) 9/67 (13.4%)
    Hearing impaired 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Hypoacusis 4/39 (10.3%) 0/28 (0%) 4/67 (6%)
    Otorrhoea 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Tinnitus 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Vertigo 4/39 (10.3%) 2/28 (7.1%) 6/67 (9%)
    Endocrine disorders
    Hyperparathyroidism 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Eye disorders
    Binocular eye movement disorder 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Blepharitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blepharospasm 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Cataract 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Chalazion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Conjunctival haemorrhage 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Conjunctival hyperaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Conjunctival oedema 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Conjunctivitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Diplopia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dry eye 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Eye discharge 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Eye pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Eye pruritus 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Eyelid oedema 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Lacrimation increased 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Ocular hyperaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ocular hypertension 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Retinopathy 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Scleral haemorrhage 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Vision blurred 1/39 (2.6%) 3/28 (10.7%) 4/67 (6%)
    Visual acuity reduced 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Visual disturbance 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Gastrointestinal disorders
    Abdominal discomfort 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Abdominal distension 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Abdominal pain 12/39 (30.8%) 3/28 (10.7%) 15/67 (22.4%)
    Abdominal pain lower 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Abdominal pain upper 4/39 (10.3%) 5/28 (17.9%) 9/67 (13.4%)
    Abdominal rigidity 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Anal fistula 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Chapped lips 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Colonic polyp 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Constipation 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Defaecation urgency 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Diarrhoea 12/39 (30.8%) 6/28 (21.4%) 18/67 (26.9%)
    Diarrhoea haemorrhagic 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Dry mouth 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dyspepsia 5/39 (12.8%) 1/28 (3.6%) 6/67 (9%)
    Dysphagia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Faecal incontinence 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Faeces pale 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Flatulence 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Gastric disorder 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Gastritis 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Gastrointestinal disorder 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Gastrooesophageal reflux disease 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Gingival pain 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Haematemesis 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Haematochezia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Haemorrhoids 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hypoaesthesia oral 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ileus 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Large intestine perforation 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Lip blister 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Lip dry 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Mouth haemorrhage 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nausea 13/39 (33.3%) 11/28 (39.3%) 24/67 (35.8%)
    Oesophagitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Oral pain 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Oral soft tissue disorder 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Peptic ulcer 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Peritonitis 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Retching 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Stomach discomfort 5/39 (12.8%) 2/28 (7.1%) 7/67 (10.4%)
    Stomatitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Toothache 6/39 (15.4%) 1/28 (3.6%) 7/67 (10.4%)
    Umbilical hernia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Uvulitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Vomiting 13/39 (33.3%) 13/28 (46.4%) 26/67 (38.8%)
    General disorders
    Adverse event 10/39 (25.6%) 3/28 (10.7%) 13/67 (19.4%)
    Asthenia 4/39 (10.3%) 4/28 (14.3%) 8/67 (11.9%)
    Axillary pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Catheter site haematoma 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Catheter site related reaction 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Chest discomfort 3/39 (7.7%) 3/28 (10.7%) 6/67 (9%)
    Chest pain 5/39 (12.8%) 4/28 (14.3%) 9/67 (13.4%)
    Chills 20/39 (51.3%) 12/28 (42.9%) 32/67 (47.8%)
    Cyst rupture 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Discomfort 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Fatigue 14/39 (35.9%) 4/28 (14.3%) 18/67 (26.9%)
    Feeling cold 5/39 (12.8%) 4/28 (14.3%) 9/67 (13.4%)
    Feeling hot 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Feeling hot and cold 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Feeling jittery 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Gait disturbance 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Influenza like illness 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Infusion site bruising 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Infusion site reaction 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Injection site thrombosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Malaise 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Oedema 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Oedema peripheral 16/39 (41%) 12/28 (42.9%) 28/67 (41.8%)
    Pain 11/39 (28.2%) 5/28 (17.9%) 16/67 (23.9%)
    Pitting oedema 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Pyrexia 17/39 (43.6%) 10/28 (35.7%) 27/67 (40.3%)
    Sensation of foreign body 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Suprapubic pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Thirst 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hepatobiliary disorders
    Cholelithiasis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Immune system disorders
    Hypersensitivity 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Seasonal allergy 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Infections and infestations
    Abscess oral 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Bronchitis 6/39 (15.4%) 3/28 (10.7%) 9/67 (13.4%)
    Bronchitis acute 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Candidiasis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Catheter related infection 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Catheter site infection 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Cellulitis 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Conjunctivitis infective 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dental caries 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Ear infection 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Fungal infection 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Gastroenteritis 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Gastroenteritis viral 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Gingival infection 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Herpes simplex 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Herpes zoster 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Implant site abscess 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Influenza 9/39 (23.1%) 3/28 (10.7%) 12/67 (17.9%)
    Kidney infection 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Labyrinthitis 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Localised infection 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Lower respiratory tract infection 8/39 (20.5%) 1/28 (3.6%) 9/67 (13.4%)
    Nail tinea 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nasopharyngitis 22/39 (56.4%) 5/28 (17.9%) 27/67 (40.3%)
    Oral candidiasis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Peritoneal infection 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Pharyngitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Pharyngitis streptococcal 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Pneumonia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Postoperative infection 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Prostate infection 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Rectal abscess 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Respiratory tract infection 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Sinusitis 5/39 (12.8%) 2/28 (7.1%) 7/67 (10.4%)
    Skin infection 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Tooth abscess 4/39 (10.3%) 0/28 (0%) 4/67 (6%)
    Tooth infection 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Upper respiratory tract infection 16/39 (41%) 7/28 (25%) 23/67 (34.3%)
    Upper respiratory tract infection bacterial 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Urinary tract infection 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Viral infection 4/39 (10.3%) 1/28 (3.6%) 5/67 (7.5%)
    Viral upper respiratory tract infection 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Injury, poisoning and procedural complications
    Arthropod bite 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Arthropod sting 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Back injury 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Contusion 5/39 (12.8%) 4/28 (14.3%) 9/67 (13.4%)
    Corneal abrasion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Electric shock 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Excoriation 7/39 (17.9%) 2/28 (7.1%) 9/67 (13.4%)
    Fall 5/39 (12.8%) 0/28 (0%) 5/67 (7.5%)
    Injury 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Joint injury 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Joint sprain 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Limb injury 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Muscle strain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Open wound 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Operative haemorrhage 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Post procedural complication 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Post procedural dizziness 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Post procedural nausea 4/39 (10.3%) 0/28 (0%) 4/67 (6%)
    Postoperative wound complication 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Procedural complication 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Procedural pain 8/39 (20.5%) 4/28 (14.3%) 12/67 (17.9%)
    Skin laceration 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Soft tissue injury 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Sunburn 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Thermal burn 2/39 (5.1%) 2/28 (7.1%) 4/67 (6%)
    Tooth fracture 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Traumatic haematoma 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Vaccination complication 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Wound 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Wound secretion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Investigations
    Aspartate aminotransferase increased 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Bacteria stool identified 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Blood alkaline phosphatase increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blood bicarbonate decreased 4/39 (10.3%) 1/28 (3.6%) 5/67 (7.5%)
    Blood bilirubin increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blood calcium decreased 4/39 (10.3%) 2/28 (7.1%) 6/67 (9%)
    Blood chloride increased 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Blood cholesterol increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blood creatinine increased 6/39 (15.4%) 1/28 (3.6%) 7/67 (10.4%)
    Blood glucose increased 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Blood parathyroid hormone increased 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Blood phosphorus decreased 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Blood potassium decreased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blood potassium increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blood pressure decreased 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Blood pressure increased 9/39 (23.1%) 4/28 (14.3%) 13/67 (19.4%)
    Blood thyroid stimulating hormone increased 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Blood triglycerides increased 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Blood urea increased 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Blood uric acid increased 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Body temperature increased 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Cardiac murmur 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Cardiac stress test abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Culture positive 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Ejection fraction decreased 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Electrocardiogram P wave abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Electrocardiogram PR shortened 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Electrocardiogram ST segment abnormal 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Electrocardiogram ST-T segment abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Electrocardiogram T wave abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Electrocardiogram T wave inversion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Electrocardiogram abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Glucose urine present 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Haematocrit decreased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Haematology test abnormal 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Haemoglobin decreased 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Heart rate decreased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Heart rate increased 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Heart rate irregular 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    International normalised ratio fluctuation 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    International normalised ratio increased 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Liver function test abnormal 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Platelet count decreased 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Platelet count increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Prostate examination abnormal 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Protein urine present 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Prothrombin time ratio increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Red blood cell count decreased 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Red blood cells urine positive 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Right ventricular systolic pressure increased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Tandem gait test abnormal 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Weight decreased 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Metabolism and nutrition disorders
    Acidosis 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Anorexia 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Decreased appetite 2/39 (5.1%) 2/28 (7.1%) 4/67 (6%)
    Dehydration 0/39 (0%) 3/28 (10.7%) 3/67 (4.5%)
    Gout 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Hyperkalaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hyperlipidaemia 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Hypocalcaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hypokalaemia 4/39 (10.3%) 2/28 (7.1%) 6/67 (9%)
    Hypomagnesaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hypophosphataemia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Metabolic acidosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Oral intake reduced 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 9/39 (23.1%) 6/28 (21.4%) 15/67 (22.4%)
    Arthritis 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Axillary mass 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Back pain 16/39 (41%) 2/28 (7.1%) 18/67 (26.9%)
    Bone pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Bunion 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Buttock pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Chest wall pain 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Flank pain 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Groin pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Intervertebral disc degeneration 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Intervertebral disc disorder 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Joint contracture 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Joint hyperextension 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Joint swelling 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Limb discomfort 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Mobility decreased 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Muscle spasms 8/39 (20.5%) 2/28 (7.1%) 10/67 (14.9%)
    Muscle tightness 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Muscle twitching 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Muscular weakness 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Musculoskeletal discomfort 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Musculoskeletal stiffness 0/39 (0%) 3/28 (10.7%) 3/67 (4.5%)
    Myalgia 8/39 (20.5%) 1/28 (3.6%) 9/67 (13.4%)
    Neck pain 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Osteopenia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Osteoporosis 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Pain in extremity 14/39 (35.9%) 7/28 (25%) 21/67 (31.3%)
    Pain in jaw 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Shoulder pain 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Tendonitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/39 (0%) 2/28 (7.1%) 2/67 (3%)
    Epithelioma 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Malignant melanoma in situ 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Skin cancer 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Nervous system disorders
    Balance disorder 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Burning sensation 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Carpal tunnel syndrome 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Coordination abnormal 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Dizziness 16/39 (41%) 5/28 (17.9%) 21/67 (31.3%)
    Dysgeusia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Encephalomalacia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Extensor plantar response 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Hand-arm vibration syndrome 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Headache 16/39 (41%) 10/28 (35.7%) 26/67 (38.8%)
    Hyperaesthesia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hyperreflexia 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Hypoaesthesia 12/39 (30.8%) 4/28 (14.3%) 16/67 (23.9%)
    Hyporeflexia 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Intracranial aneurysm 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Ischaemic stroke 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Lethargy 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Loss of consciousness 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Memory impairment 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nerve compression 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nystagmus 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Paraesthesia 19/39 (48.7%) 3/28 (10.7%) 22/67 (32.8%)
    Restless legs syndrome 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Sciatica 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Somnolence 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Syncope 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Tremor 4/39 (10.3%) 0/28 (0%) 4/67 (6%)
    Psychiatric disorders
    Agitation 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Alcoholism 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Anxiety 4/39 (10.3%) 1/28 (3.6%) 5/67 (7.5%)
    Confusional state 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Depressed mood 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Depression 4/39 (10.3%) 1/28 (3.6%) 5/67 (7.5%)
    Emotional distress 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Insomnia 4/39 (10.3%) 4/28 (14.3%) 8/67 (11.9%)
    Major depression 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Mood altered 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nervousness 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Panic attack 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Restlessness 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Sleep disorder 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Renal and urinary disorders
    Azotaemia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dysuria 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Haematuria 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Micturition disorder 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Micturition urgency 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nocturia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Proteinuria 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Renal failure 1/39 (2.6%) 3/28 (10.7%) 4/67 (6%)
    Renal failure chronic 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Renal impairment 6/39 (15.4%) 3/28 (10.7%) 9/67 (13.4%)
    Urethral meatus stenosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Urethral stricture 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Urinary incontinence 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Urinary retention 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Reproductive system and breast disorders
    Breast discharge 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Breast discomfort 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dysmenorrhoea 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Nipple pain 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Penile discharge 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Prostatitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Scrotal angiokeratoma 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Respiratory, thoracic and mediastinal disorders
    Allergic cough 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Asthma 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Atelectasis 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Bronchial hyperactivity 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Bronchospasm 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Chronic obstructive pulmonary disease 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Cough 20/39 (51.3%) 8/28 (28.6%) 28/67 (41.8%)
    Dysphonia 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dyspnoea 4/39 (10.3%) 1/28 (3.6%) 5/67 (7.5%)
    Dyspnoea exacerbated 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Epistaxis 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Nasal congestion 11/39 (28.2%) 3/28 (10.7%) 14/67 (20.9%)
    Paranasal sinus hypersecretion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Pharyngolaryngeal pain 13/39 (33.3%) 4/28 (14.3%) 17/67 (25.4%)
    Pleural rub 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Pneumothorax 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Productive cough 2/39 (5.1%) 2/28 (7.1%) 4/67 (6%)
    Pulmonary hypertension 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Respiratory tract congestion 5/39 (12.8%) 2/28 (7.1%) 7/67 (10.4%)
    Rhinitis allergic 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Rhinorrhoea 6/39 (15.4%) 3/28 (10.7%) 9/67 (13.4%)
    Rhonchi 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Sinus congestion 7/39 (17.9%) 1/28 (3.6%) 8/67 (11.9%)
    Sleep apnoea syndrome 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Throat irritation 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Throat tightness 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Upper respiratory tract congestion 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Wheezing 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Skin and subcutaneous tissue disorders
    Acne 1/39 (2.6%) 1/28 (3.6%) 2/67 (3%)
    Angiokeratoma 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Angioneurotic oedema 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Anhidrosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Blister 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Cold sweat 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Decubitus ulcer 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Dermal cyst 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dermatitis bullous 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Dermatitis contact 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Dry skin 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Ecchymosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Erythema 2/39 (5.1%) 3/28 (10.7%) 5/67 (7.5%)
    Hair growth abnormal 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Hyperhidrosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Pruritus 7/39 (17.9%) 3/28 (10.7%) 10/67 (14.9%)
    Pruritus allergic 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Pruritus generalised 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Psoriasis 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Rash 6/39 (15.4%) 2/28 (7.1%) 8/67 (11.9%)
    Rash erythematous 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Rash maculo-papular 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Rash papular 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Rash pruritic 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Seborrhoeic dermatitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Skin discolouration 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Skin disorder 3/39 (7.7%) 0/28 (0%) 3/67 (4.5%)
    Skin irritation 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Skin lesion 1/39 (2.6%) 2/28 (7.1%) 3/67 (4.5%)
    Skin nodule 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Skin ulcer 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Urticaria 3/39 (7.7%) 4/28 (14.3%) 7/67 (10.4%)
    Vascular skin disorder 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Yellow skin 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Vascular disorders
    Arterial stenosis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Atherosclerosis 0/39 (0%) 1/28 (3.6%) 1/67 (1.5%)
    Flushing 2/39 (5.1%) 2/28 (7.1%) 4/67 (6%)
    Haematoma 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Hot flush 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Hypertension 5/39 (12.8%) 2/28 (7.1%) 7/67 (10.4%)
    Hypotension 3/39 (7.7%) 1/28 (3.6%) 4/67 (6%)
    Labile hypertension 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Lymphoedema 2/39 (5.1%) 0/28 (0%) 2/67 (3%)
    Orthostatic hypotension 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Pallor 2/39 (5.1%) 2/28 (7.1%) 4/67 (6%)
    Peripheral coldness 2/39 (5.1%) 1/28 (3.6%) 3/67 (4.5%)
    Phlebitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Raynaud's phenomenon 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Steal syndrome 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Vascular pseudoaneurysm 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Vasculitis 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)
    Venous insufficiency 1/39 (2.6%) 0/28 (0%) 1/67 (1.5%)

    Limitations/Caveats

    No valid conclusions can be made from the predefined primary efficacy analysis. The sponsor believes that it is more statistically appropriate to compare placebo patients with Fabrazyme patients as they were randomized in the original Phase 4 trial.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    In multi-site studies, Principal Investigator (PI) can publish after Genzyme publishes or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.

    Results Point of Contact

    Name/Title Genzyme Medical Information
    Organization Genzyme Corporation
    Phone 800-745-4447
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00081497
    Other Study ID Numbers:
    • AGAL02503
    First Posted:
    Apr 16, 2004
    Last Update Posted:
    Apr 2, 2015
    Last Verified:
    Mar 1, 2015