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SCOUT: A Long Term Study of Sibutramine and the Role of Obesity Management in Relation to Cardiovascular Disease in Overweight and Obese Patients

Sponsor
Abbott (Industry)
Overall Status
Completed
CT.gov ID
NCT00234832
Collaborator
(none)
10,777
Enrollment
1
Location
3
Arms
82
Duration (Months)
131.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study was to determine the long-term effect of sibutramine treatment on cardiovascular outcomes in overweight and obese patients at risk of a cardiovascular event.

Condition or Disease Intervention/Treatment Phase
  • Drug: Sibutramine hydrochloride
  • Drug: Placebo
  • Drug: Sibutramine hydrochloride
 Phase 3

Detailed Description

The study consisted of 4 periods: 1) a Screening Period of approximately 2 weeks; 2) a 6-week Lead-in Period, during which subjects received single-blind sibutramine and country-specific standard of care for weight management. Subjects who discontinued study drug treatment during the Lead-in Period were not randomized and did not participate in the double-blind Treatment Period or the Follow-up Period; 3) a double-blind Treatment Period in which subjects were randomized to 1 of the 2 treatment groups and were followed until the study ended; and 4) a double-blind Follow-up Period, during which randomized subjects who discontinued study drug were followed until the study ended. The Randomization Phase consisted of the double-blind Treatment Period and the double-blind Follow-up Period. Subjects received country-specific standard of care for weight management during the Randomization Phase.

An independent events adjudication committee evaluated all potential cardiovascular outcome events and confirmed the outcome events and time of onset to be included in the statistical analyses.

Study Design

Study Type:
Interventional
Actual Enrollment :
10777 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Sibutramine Cardiovascular Morbidity/Mortality Outcomes Study in Overweight or Obese Subjects at Risk of a Cardiovascular Event
Study Start Date :
Jan 1, 2003
Actual Primary Completion Date :
Mar 1, 2009
Actual Study Completion Date :
Nov 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sibutramine

Subjects were randomized to receive sibutramine 10 mg once daily (QD) during the Treatment Period after a 6-week Lead-in Period

Drug: Sibutramine hydrochloride
One 10 mg tablet QD plus country-specific standard care for weight management. (During the Treatment Period, the dose could have been titrated up to 15 mg at the investigator's discretion.)
Other Names:
  • ABT-991
  • sibutramine
  • Meridia
  • Reductil

    		•
    Placebo Comparator: Placebo

    Subjects were randomized to receive placebo QD during the Treatment Period after a 6-week Lead-in Period

    Drug: Placebo
    1 tablet QD plus country-specific standard care for weight management (During the Treatment Period, the dose could have been titrated up to 15 mg at the investigator's discretion.)
    Experimental: Lead-in sibutramine

    All subjects received 10 mg sibutramine QD during a 6-week Lead-in Period

    Drug: Sibutramine hydrochloride
    10 mg tablet QD during the 6-week Lead-in Period plus country-specific standard care for weight management

    Outcome Measures

    Primary Outcome Measures

    1. Risk of Experiencing a Primary Outcome Event (POE) (i.e., Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, Resuscitated Cardiac Arrest, Cardiovascular [CV] Death) [From randomization up to 6 years]

      For each subject, POE status (with/without an event) and time to first occurrence of a POE using time-to-event analysis were evaluated. All POE confirmed by an independent adjudication committee were included in the analysis.

    Secondary Outcome Measures

    1. Risk of Death From Any Cause (All-cause Mortality) [From randomization up to 6 years]

      For each subject who died, the time to death was evaluated using time-to-event analysis.

    2. Risk of Experiencing a POE or a Revascularization Procedure [From randomization up to 6 years]

      This outcome includes nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, CV death (including events such as fatal MI and fatal stroke), and any of the following revascularization procedures: percutaneous transluminal coronary angioplasty, coronary artery bypass graft, coronary artery stent placement, cardiac transplant, peripheral vascular bypass or angioplasty, and carotid endarterectomy. For each subject, the POE or revascularization status (yes/no) and time to first occurrence of an event using time-to-event analysis were evaluated.

    3. Risk of Experiencing a Nonfatal MI Included in the POE [From randomization up to 6 years]

      For each subject, the first occurrence of a nonfatal MI included in the POE was evaluated using time-to-event analysis.

    4. Risk of Experiencing a Nonfatal Stroke Included in the POE [From randomization up to 6 years]

      For each subject, the time to first occurrence of a nonfatal stroke included in the POE was evaluated using time-to-event analysis.

    5. Risk of Experiencing a Resuscitated Cardiac Arrest Included in the POE [From randomization up to 6 years]

      For each subject, the time to first occurrence of a resuscitated cardiac arrest included in the POE was evaluated using time-to-event analysis.

    6. Risk of Experiencing Cardiovascular Death Included in the POE [From randomization up to 6 years]

      For each subject, the time to cardiovascular death included in the POE was evaluated using time-to-event analysis.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subject's body mass index (BMI) was >= 27 kg/m(2) and <= 45 kg/m(2) or their BMI was

    = 25 kg/m(2) and < 27 kg/m(2) with waist circumference of >= 102 cm in males or >= 88 cm in females.

    • Medical history positive for:

    • Preexisting cardiovascular disease (i.e., coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease) and/or

    • Type 2 diabetes mellitus with at least 1 other risk factor (i.e., dyslipidemia, controlled hypertension, current smoker, or diabetic nephropathy with evidence of microalbuminuria)

    Exclusion Criteria:

    • History of recent myocardial infarction.

    • Heart failure symptoms greater than New York Heart Association Functional Class II.

    • Hemodynamically significant valvular or left ventricular (LV) tract obstruction.

    • Subjects without a pacemaker and with any of the following:

    • Sinus bradycardia (< 50 bpm)

    • Sick sinus syndrome

    • Atrioventricular block of more than 1st degree

    • Mean sitting systolic blood pressure (SBP) > 160 mmHg. Mean sitting diastolic blood pressure (DBP) > 100 mmHg. Mean sitting heart rate (HR) > 100 bpm.

    • Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias.

    • Planned cardiac surgery or coronary angioplasty within 6 months of screening.

    • History of recent non-hemorrhagic stroke or transient ischemic attack (TIA), history of hemorrhagic stroke.

    • Hyperthyroidism.

    • Known chronic liver disease or endstage renal disease.

    • Severe, symptomatic benign prostatic hyperplasia which may require surgery.

    • Known pheochromocytoma, history of narrow angle glaucoma, Gilles de la Tourette syndrome, history of seizures, history of bariatric or abdominal obesity surgery (excluding liposuction).

    • Concomitant use of monoamine oxidase inhibitors or drugs that increase levels of serotonin in the brain.

    • Treated hypertension stabilized for less than 3 months.

    • Inability to perform regular physical activity.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Global Medical Services North Chicago Illinois United States 60064

    Sponsors and Collaborators

    • Abbott

    Investigators

    • Study Director: Cheryl Renz, MD, Abbott

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00234832
    Other Study ID Numbers:
    • M01-392
    First Posted:
    Oct 10, 2005
    Last Update Posted:
    May 11, 2010
    Last Verified:
    May 1, 2010
    Keywords provided by , ,
    Obesity
    Sibutramine
    Additional relevant MeSH terms:
    Obesity
    Overweight
    Sibutramine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Of the 10777 subjects enrolled into the study, 33 were not treated with Lead-in Period sibutramine. Of the 10744 subjects who took at least 1 dose of Lead-in Period sibutramine, 939 were not randomized. One of the remaining 9805 subjects was not dispensed randomized study drug and was not included in the intent-to-treat population (N = 9804).
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Period Title: Overall Study
    STARTED 4906 4898
    COMPLETED 3890 3902
    NOT COMPLETED 1016 996

    Baseline Characteristics

    Arm/Group Title Randomized Sibutramine Randomized Placebo Total
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Total of all reporting groups
    Overall Participants 4906 4898 9804
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3040
    62%
    2997
    61.2%
    6037
    61.6%
    >=65 years
    1866
    38%
    1901
    38.8%
    3767
    38.4%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.2
    (6.09)
    63.3
    (6.15)
    63.2
    (6.12)
    Sex: Female, Male (Count of Participants)
    Female
    2099
    42.8%
    2055
    42%
    4154
    42.4%
    Male
    2807
    57.2%
    2843
    58%
    5650
    57.6%
    Region of Enrollment (participants) [Number]
    Europe
    4160
    84.8%
    4150
    84.7%
    8310
    84.8%
    Australia
    384
    7.8%
    385
    7.9%
    769
    7.8%
    Brazil
    233
    4.7%
    234
    4.8%
    467
    4.8%
    Mexico
    129
    2.6%
    129
    2.6%
    258
    2.6%
    Cardiovascular (CV) risk group status (Number) [Number]
    DM only
    1207
    24.6%
    1178
    24.1%
    2385
    24.3%
    CV only
    759
    15.5%
    793
    16.2%
    1552
    15.8%
    CV + DM
    2906
    59.2%
    2901
    59.2%
    5807
    59.2%
    Unknown CV risk group status
    34
    0.7%
    26
    0.5%
    60
    0.6%

    Outcome Measures

    1. Primary Outcome
    Title Risk of Experiencing a Primary Outcome Event (POE) (i.e., Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, Resuscitated Cardiac Arrest, Cardiovascular [CV] Death)
    Description For each subject, POE status (with/without an event) and time to first occurrence of a POE using time-to-event analysis were evaluated. All POE confirmed by an independent adjudication committee were included in the analysis.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on intent-to-treat (ITT) population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized. Subjects were also categorized into 1 of 3 prespecified CV risk groups: diabetes mellitus (DM) only, CV only, and CV + DM.
    Arm/Group Title Randomized Sibutramine Randomized Placebo DM Only Randomized to Sibutramine DM Only Randomized to Placebo CV Only Randomized to Sibutramine CV Only Randomized to Placebo CV + DM Randomized to Sibutramine CV + DM Randomized to Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects with a history of type 2 DM with at least one other risk factor (i.e., hypertension controlled on medication, dyslipidemia, current cigarette smoking, diabetic nephropathy with evidence of microalbuminuria), but no history of coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. Subjects with a history of type 2 DM with at least one other risk factor (i.e., hypertension controlled on medication, dyslipidemia, current cigarette smoking, diabetic nephropathy with evidence of microalbuminuria), but no history of coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. Subjects with a history of coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease, but no history of type 2 DM with at least one other risk factor who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. Subjects with a history of coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease, but no history of type 2 DM with at least one other risk factor who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. Subjects with a history of coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease, and with a history of type 2 DM with at least one other risk factor who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. Subjects with a history of coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease, and with a history of type 2 DM with at least one other risk factor who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management.
    Measure Participants 4906 4898 1207 1178 759 793 2906 2901
    Intent-to-treat population
    561
    11.4%
    490
    10%
    79
    0.8%
    77
    NaN
    77
    NaN
    66
    NaN
    403
    NaN
    346
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments For the sample size calculation, a two-tailed alpha level of 0.05 was used along with power of 90%. The annual composite event rate in the placebo arm was assumed to be 7.0%. A sample of 3983 subjects in each of the 2 groups, corrected for a 30% noncompliance rate (15% in Year 1 and 6.3% in each year, Years 2 to 4), followed for at least 3 years was expected to have 90% power to detect a relative risk reduction of 15% with sibutramine relative to placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments No adjustment for multiple testing or interim analysis was performed. The primary outcome was tested at a 2-sided alpha level of 0.05.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.162
    Confidence Interval (2-Sided) 95%
    1.029 to 1.311
    Parameter Dispersion Type:
    Value:
    Estimation Comments The Cox model included factors for treatment, country, gender, and age (continuous) at Lead-in Period baseline. For the calculation of risk, the sibutramine arm is the numerator and the placebo arm is the denominator.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection DM Only Randomized to Sibutramine, DM Only Randomized to Placebo
    Comments This analysis included only subjects with DM only in a comparison of sibutramine and placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.948
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.010
    Confidence Interval (2-Sided) 95%
    0.738 to 1.384
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection CV Only Randomized to Sibutramine, CV Only Randomized to Placebo
    Comments This analysis included only subjects with CV only in a comparison of sibutramine and placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.149
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.276
    Confidence Interval (2-Sided) 95%
    0.916 to 1.776
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection CV + DM Randomized to Sibutramine, CV + DM Randomized to Placebo
    Comments This analysis included only subjects with CV + DM in a comparison of sibutramine and placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.182
    Confidence Interval (2-Sided) 95%
    1.024 to 1.365
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Risk of Death From Any Cause (All-cause Mortality)
    Description For each subject who died, the time to death was evaluated using time-to-event analysis.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on ITT population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized.
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Measure Participants 4906 4898
    Number [Participants]
    418
    8.5%
    404
    8.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.543
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.043
    Confidence Interval (2-Sided) 95%
    0.910 to 1.196
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Risk of Experiencing a POE or a Revascularization Procedure
    Description This outcome includes nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, CV death (including events such as fatal MI and fatal stroke), and any of the following revascularization procedures: percutaneous transluminal coronary angioplasty, coronary artery bypass graft, coronary artery stent placement, cardiac transplant, peripheral vascular bypass or angioplasty, and carotid endarterectomy. For each subject, the POE or revascularization status (yes/no) and time to first occurrence of an event using time-to-event analysis were evaluated.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on ITT population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized.
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Measure Participants 4906 4898
    Number [Participants]
    927
    18.9%
    856
    17.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.051
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.097
    Confidence Interval (2-Sided) 95%
    0.999 to 1.204
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Risk of Experiencing a Nonfatal MI Included in the POE
    Description For each subject, the first occurrence of a nonfatal MI included in the POE was evaluated using time-to-event analysis.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on ITT population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized.
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Measure Participants 4906 4898
    Number [Participants]
    200
    4.1%
    159
    3.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.276
    Confidence Interval (2-Sided) 95%
    1.036 to 1.571
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Risk of Experiencing a Nonfatal Stroke Included in the POE
    Description For each subject, the time to first occurrence of a nonfatal stroke included in the POE was evaluated using time-to-event analysis.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on ITT population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized.
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Measure Participants 4906 4898
    Number [Participants]
    127
    2.6%
    95
    1.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.025
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.355
    Confidence Interval (2-Sided) 95%
    1.038 to 1.767
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Risk of Experiencing a Resuscitated Cardiac Arrest Included in the POE
    Description For each subject, the time to first occurrence of a resuscitated cardiac arrest included in the POE was evaluated using time-to-event analysis.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on ITT population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized.
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Measure Participants 4906 4898
    Number [Participants]
    11
    0.2%
    7
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.343
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 1.582
    Confidence Interval (2-Sided) 95%
    0.613 to 4.081
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Risk of Experiencing Cardiovascular Death Included in the POE
    Description For each subject, the time to cardiovascular death included in the POE was evaluated using time-to-event analysis.
    Time Frame From randomization up to 6 years

    Outcome Measure Data

    Analysis Population Description
    Analysis based on ITT population, which consists of all randomized subjects dispensed randomized study drug and grouped according to the intervention to which they were randomized.
    Arm/Group Title Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed sibutramine during the Treatment Period and continued standard care for weight management. If sibutramine was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period. Subjects who completed the 6-week Lead-in Period and who were randomized and dispensed placebo during the Treatment Period and continued standard care for weight management. If placebo was prematurely discontinued, subjects continued standard care for weight management during the Follow-up Period.
    Measure Participants 4906 4898
    Number [Participants]
    223
    4.5%
    229
    4.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Randomized Sibutramine, Randomized Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.899
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.988
    Confidence Interval (2-Sided) 95%
    0.822 to 1.188
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Treatment-emergent serious adverse events (SAE) were defined as those that began on or after the first dose of randomized study drug (sibutramine or placebo) during the Randomization Phase through 30 days after the last dose.
    Adverse Event Reporting Description SAEs confirmed to be outcome events are included. Lead-in Period SAEs occurring on or after the first dose of sibutramine during the Lead-in Period through 30 days after the last dose of sibutramine for subjects who discontinued or through 30 days into the Randomization Phase for subjects who were randomized are included.
    Arm/Group Title Lead-in Period Sibutramine Randomized Sibutramine Randomized Placebo
    Arm/Group Description Subjects who received sibutramine 10 mg QD plus standard care for weight management during a 6-week Lead-in Period. Subjects who successfully completed a 6-week Lead-in Period and who were randomized to receive sibutramine plus standard care for weight management during the Treatment Period of the Randomization Phase, and if sibutramine was prematurely discontinued, they received standard care for weight management during the Follow-up Period of the Randomization Phase. Subjects who successfully completed a 6-week Lead-in Period and who were randomized to receive placebo plus standard care for weight management during the Treatment Period of the Randomizaiton Phase, and if placebo was prematurely discontinued, they received standard care for weight management during the Follow-up Period of the Randomization Phase.
    All Cause Mortality
    Lead-in Period Sibutramine Randomized Sibutramine Randomized Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Lead-in Period Sibutramine Randomized Sibutramine Randomized Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 425/10744 (4%) 2063/4904 (42.1%) 1977/4881 (40.5%)
    Blood and lymphatic system disorders
    Anemia 0/10744 (0%) 19/4904 (0.4%) 11/4881 (0.2%)
    Bicytopenia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Coagulopathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Disseminated intravascular coagulation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hemolytic anemia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hemorrhagic anemia 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Hemorrhagic disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypersplenism 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hypochromic anemia 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Hypoprothrombinanemia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Idiopathic thrombocytopenic purpura 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Iron deficiency anemia 0/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Leukocytosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lymphadenitis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Lymphadenopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lymphatic obstruction 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Lymphocytosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Microcytic anemia 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Neutropenia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Normochromic normocytic anemia 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Thrombocytopenia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Thrombocytosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cardiac disorders
    Acute coronary syndrome 6/10744 (0.1%) 25/4904 (0.5%) 26/4881 (0.5%)
    Acute left ventricular failure 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Acute myocardial infarction 3/10744 (0%) 87/4904 (1.8%) 87/4881 (1.8%)
    Adams-Stokes syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Angina pectoris 21/10744 (0.2%) 111/4904 (2.3%) 133/4881 (2.7%)
    Angina unstable 23/10744 (0.2%) 122/4904 (2.5%) 104/4881 (2.1%)
    Aortic valve disease 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Aortic valve disease mixed 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Aortic valve incompetence 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Aortic valve stenosis 0/10744 (0%) 7/4904 (0.1%) 9/4881 (0.2%)
    Arrhythmia 0/10744 (0%) 0/4904 (0%) 6/4881 (0.1%)
    Arrhythmia supraventricular 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Arteriosclerosis coronary artery 0/10744 (0%) 4/4904 (0.1%) 8/4881 (0.2%)
    Atrial fibrillation 20/10744 (0.2%) 115/4904 (2.3%) 135/4881 (2.8%)
    Atrial flutter 4/10744 (0%) 21/4904 (0.4%) 29/4881 (0.6%)
    Atrial tachycardia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Atrial thrombosis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Atrioventricular block 1/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Atrioventricular block complete 2/10744 (0%) 8/4904 (0.2%) 16/4881 (0.3%)
    Atrioventricular block first degree 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Atrioventricular block second degree 0/10744 (0%) 3/4904 (0.1%) 16/4881 (0.3%)
    Bradyarrhythmia 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Bradycardia 1/10744 (0%) 7/4904 (0.1%) 7/4881 (0.1%)
    Bundle branch block right 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cardiac aneurysm 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Cardiac arrest 0/10744 (0%) 24/4904 (0.5%) 14/4881 (0.3%)
    Cardiac asthma 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cardiac disorder 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cardiac failure 2/10744 (0%) 82/4904 (1.7%) 80/4881 (1.6%)
    Cardiac failure acute 0/10744 (0%) 3/4904 (0.1%) 9/4881 (0.2%)
    Cardiac failure chronic 0/10744 (0%) 5/4904 (0.1%) 8/4881 (0.2%)
    Cardiac failure congestive 3/10744 (0%) 53/4904 (1.1%) 41/4881 (0.8%)
    Cardiac tamponade 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Cardio-respiratory arrest 1/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Cardiogenic shock 0/10744 (0%) 4/4904 (0.1%) 5/4881 (0.1%)
    Cardiomyopathy 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cardiopulmonary failure 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Cardiovascular insufficiency 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Chronic right ventricular failure 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Conduction disorder 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Congestive cardiomyopathy 1/10744 (0%) 7/4904 (0.1%) 6/4881 (0.1%)
    Cor pulmonale chronic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Coronary artery disease 15/10744 (0.1%) 135/4904 (2.8%) 118/4881 (2.4%)
    Coronary artery dissection 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Coronary artery insufficiency 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Coronary artery occlusion 1/10744 (0%) 3/4904 (0.1%) 8/4881 (0.2%)
    Coronary artery stenosis 4/10744 (0%) 76/4904 (1.5%) 74/4881 (1.5%)
    Coronary artery thrombosis 1/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Diastolic dysfunction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Extrasystoles 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypertensive cardiomyopathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypertensive heart disease 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Intracardiac thrombus 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Ischemic cardiomyopathy 0/10744 (0%) 10/4904 (0.2%) 13/4881 (0.3%)
    Left ventricular dysfunction 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Left ventricular failure 1/10744 (0%) 10/4904 (0.2%) 16/4881 (0.3%)
    Left ventricular hypertrophy 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Mitral valve incompetence 0/10744 (0%) 4/4904 (0.1%) 6/4881 (0.1%)
    Mitral valve stenosis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Myocardial infarction 11/10744 (0.1%) 87/4904 (1.8%) 80/4881 (1.6%)
    Myocardial ischemia 5/10744 (0%) 57/4904 (1.2%) 36/4881 (0.7%)
    Nodal arrhythmia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Palpitations 3/10744 (0%) 2/4904 (0%) 6/4881 (0.1%)
    Pericardial effusion 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Pericarditis 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Postinfarction angina 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Prinzmetal angina 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Right ventricular failure 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Sick sinus syndrome 2/10744 (0%) 11/4904 (0.2%) 12/4881 (0.2%)
    Silent myocardial infarction 0/10744 (0%) 5/4904 (0.1%) 4/4881 (0.1%)
    Sinoatrial block 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Sinus arrhythmia 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Sinus bradycardia 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Sinus tachycardia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Subendocardial ischemia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Supraventricular extrasystoles 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Supraventricular tachyarrhythmia 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Supraventricular tachycardia 3/10744 (0%) 12/4904 (0.2%) 6/4881 (0.1%)
    Tachyarrhythmia 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Tachycardia 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Torsade de pointes 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Tricuspid valve incompetence 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Trifascicular block 2/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Ventricular arrhythmia 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Ventricular extrasystoles 0/10744 (0%) 7/4904 (0.1%) 2/4881 (0%)
    Ventricular failure 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Ventricular fibrillation 2/10744 (0%) 5/4904 (0.1%) 6/4881 (0.1%)
    Ventricular tachyarrhythmia 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Ventricular tachycardia 1/10744 (0%) 25/4904 (0.5%) 18/4881 (0.4%)
    Congenital, familial and genetic disorders
    Atrial septal defect 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Congenital cystic kidney disease 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Congenital spondylolithesis 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Dysplastic naevus syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastrointestinal angiodysplasia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastrointestinal angiodysplasia hemorrhagic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hydrocele 2/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Phimosis 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Ear and labyrinth disorders
    Acute vestibular syndrome 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Aural polyp 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Deafness unilateral 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hearing impaired 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypoacusis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neurosensory hypoacusis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Sudden hearing loss 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vertigo 1/10744 (0%) 4/4904 (0.1%) 5/4881 (0.1%)
    Vertigo positional 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Vestibular disorder 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Endocrine disorders
    Autoimmune thyroiditis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Goiter 0/10744 (0%) 7/4904 (0.1%) 6/4881 (0.1%)
    Hyperparathyroidism 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Hyperparathyroidism primary 1/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Hyperthyroidism 0/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Hypothyroidism 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Inappropriate antidiuretic hormone secretion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Myxedema 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Toxic nodular goiter 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Eye disorders
    Amaurosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Angle closure glaucoma 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Aphakia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cataract 4/10744 (0%) 33/4904 (0.7%) 29/4881 (0.6%)
    Cataract diabetic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cataract nuclear 1/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Cataract subcapsular 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Diabetic retinopathy 0/10744 (0%) 6/4904 (0.1%) 4/4881 (0.1%)
    Diplopia 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Extraocular muscle paresis 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Eye hemorrhage 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Eye pain 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Glaucoma 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Iris bombe 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Keratitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lens dislocation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Macular hole 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Macular edema 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Maculopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ocular myasthenia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ocular vascular disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Open-angle glaucoma 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Optic ischemic neuropathy 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Punctate keratitis 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Retinal artery occlusion 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Retinal detachment 0/10744 (0%) 10/4904 (0.2%) 5/4881 (0.1%)
    Retinal hemorrhage 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Retinal vein occlusion 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Retinal vein thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Strabismus 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Synchysis scintillans 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Ulcerative keratitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Uveitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Visual impairment 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vitreous detachment 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Vitreous disorder 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Vitreous hemorrhage 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Gastrointestinal disorders
    Abdominal distension 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Abdominal hernia 0/10744 (0%) 7/4904 (0.1%) 3/4881 (0.1%)
    Abdominal hernia obstructive 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Abdominal mass 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Abdominal pain 0/10744 (0%) 8/4904 (0.2%) 9/4881 (0.2%)
    Abdominal pain lower 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Abdominal pain upper 0/10744 (0%) 2/4904 (0%) 6/4881 (0.1%)
    Abdominal strangulated hernia 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Anal fissure 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Anal fistula 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Anal stenosis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Anal ulcer 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Barrett's esophagus 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cecitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Change of bowel habit 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Celiac artery stenosis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Colitis 0/10744 (0%) 5/4904 (0.1%) 0/4881 (0%)
    Colitis ischemic 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Colonic polyp 2/10744 (0%) 3/4904 (0.1%) 10/4881 (0.2%)
    Constipation 1/10744 (0%) 5/4904 (0.1%) 4/4881 (0.1%)
    Diabetic gastroparesis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diarrhea 0/10744 (0%) 4/4904 (0.1%) 7/4881 (0.1%)
    Diarrhea hemorrhagic 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Diverticulitis intestinal hemorrhagic 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diverticulum 1/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Diverticulum intestinal 0/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Diverticulum intestinal hemorrhagic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Duodenal ulcer 1/10744 (0%) 5/4904 (0.1%) 4/4881 (0.1%)
    Duodenal ulcer hemorrhage 0/10744 (0%) 12/4904 (0.2%) 2/4881 (0%)
    Duodenal ulcer perforation 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Duodenitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Dyspepsia 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Enteritis 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Enterocolitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Erosive esophagitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Fecal incontinence 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Fecaloma 1/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Food poisoning 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Gastric hemorrhage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gastric mucosal lesion 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gastric perforation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gastric polyps 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Gastric ulcer 3/10744 (0%) 5/4904 (0.1%) 7/4881 (0.1%)
    Gastric ulcer hemorrhage 0/10744 (0%) 9/4904 (0.2%) 9/4881 (0.2%)
    Gastritis 0/10744 (0%) 8/4904 (0.2%) 4/4881 (0.1%)
    Gastritis atrophic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastritis erosive 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Gastritis hemorrhagic 1/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Gastroduodenitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastrointestinal disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastrointestinal hemorrhage 0/10744 (0%) 3/4904 (0.1%) 4/4881 (0.1%)
    Gastrointestinal inflammation 2/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Gastrointestinal ulcer hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastroesophageal reflux disease 0/10744 (0%) 4/4904 (0.1%) 6/4881 (0.1%)
    Gastroesophageal sphincter insufficiency 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gastroesophagitis 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gingival pain 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hematochezia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hemorrhagic erosive gastritis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hemorrhoidal hemorrhage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hemorrhoids 1/10744 (0%) 3/4904 (0.1%) 4/4881 (0.1%)
    Hernial eventration 0/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Hiatus hernia 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Ileitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ileus 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Ileus paralytic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Impaired gastric emptying 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Inguinal hernia 4/10744 (0%) 13/4904 (0.3%) 18/4881 (0.4%)
    Intestinal ischemia 0/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Intestinal obstruction 0/10744 (0%) 6/4904 (0.1%) 3/4881 (0.1%)
    Intra-abdominal hematoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Irritable bowel syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Large intestinal obstruction 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Large intestine perforation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lower gastrointestinal hemorrhage 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Mechanical ileus 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Melena 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Melanosis coli 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Mesenteric artery stenosis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Mesenteric artery thrombosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Mesenteric occlusion 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Nausea 0/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Esophageal stenosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Esophageal ulcer hemorrhage 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Esophagitis 3/10744 (0%) 5/4904 (0.1%) 1/4881 (0%)
    Esophagitis ulcerative 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pancreatitis 1/10744 (0%) 3/4904 (0.1%) 4/4881 (0.1%)
    Pancreatitis acute 0/10744 (0%) 3/4904 (0.1%) 14/4881 (0.3%)
    Pancreatitis chronic 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Pancreatitis necrotizing 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Papilla of Vater stenosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Peptic ulcer 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Peptic ulcer hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Periodontal disease 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Peritoneal adhesions 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Peritoneal hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Peritonitis 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Proctitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Rectal hemorrhage 1/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Rectal perforation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Rectal polyp 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Rectal prolapse 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Reflux esophagitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Retroperitoneal fibrosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Retroperitoneal hematoma 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Small intestinal hemorrhage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Small intestinal obstruction 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Subileus 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Tongue hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Tooth disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Tooth loss 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Umbilical hernia 0/10744 (0%) 12/4904 (0.2%) 9/4881 (0.2%)
    Umbilical hernia, obstructive 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Upper gastrointestinal hemorrhage 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Varices esophageal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vomiting 0/10744 (0%) 1/4904 (0%) 5/4881 (0.1%)
    General disorders
    Abasia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Adhesion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Adverse drug reaction 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Asthenia 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Catheter-related complication 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Chest discomfort 1/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Chest pain 5/10744 (0%) 22/4904 (0.4%) 18/4881 (0.4%)
    Chills 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Cyst 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Death 17/10744 (0.2%) 25/4904 (0.5%) 18/4881 (0.4%)
    Drug intolerance 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Dysplasia 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Fatigue 1/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Foaming at mouth 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    General physical health deterioration 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hernia obstructive 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Impaired healing 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Implant expulsion 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Implant site fibrosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Implant site inflammation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Inflammation 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Malaise 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Mechanical complication of implant 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Metaplasia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Multi-organ failure 1/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Necrosis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Non-cardiac chest pain 2/10744 (0%) 19/4904 (0.4%) 15/4881 (0.3%)
    Pain 2/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Peripheral edema 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Pyrexia 0/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Sudden cardiac death 0/10744 (0%) 11/4904 (0.2%) 4/4881 (0.1%)
    Sudden death 3/10744 (0%) 19/4904 (0.4%) 26/4881 (0.5%)
    Swelling 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bile duct stone 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hepatic lesion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hepatobiliary disorders
    Autoimmune hepatitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bile duct obstruction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bile duct stenosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Biliary cirrhosis primary 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Biliary colic 1/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Cholangitis 0/10744 (0%) 1/4904 (0%) 4/4881 (0.1%)
    Cholangitis acute 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cholecystitis 2/10744 (0%) 8/4904 (0.2%) 7/4881 (0.1%)
    Cholecystitis acute 0/10744 (0%) 7/4904 (0.1%) 5/4881 (0.1%)
    Cholecystitis chronic 0/10744 (0%) 1/4904 (0%) 4/4881 (0.1%)
    Cholelithiasis 2/10744 (0%) 26/4904 (0.5%) 25/4881 (0.5%)
    Cirrhosis alcoholic 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gallbladder cholesterolosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gallbladder disorder 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gallbladder obstruction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gallbladder perforation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hepatic cirrhosis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Hepatic mass 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hepatitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hepatitis acute 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hepatorenal failure 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Liver disorder 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Liver injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Immune system disorders
    Anaphylactic reaction 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Anaphylactic shock 1/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Hypersensitivity 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Infections and infestations
    Abdominal abscess 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Abscess limb 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Abscess neck 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Abscess oral 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Acarodermatitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Anal abscess 1/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Appendicitis 0/10744 (0%) 6/4904 (0.1%) 3/4881 (0.1%)
    Appendicitis perforated 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Arteriosclerotic gangrene 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Arthritis bacterial 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Arthritis infective 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bacterial infection 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bacterial pyelonephritis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Biliary sepsis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Bronchiectasis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bronchitis 0/10744 (0%) 13/4904 (0.3%) 15/4881 (0.3%)
    Bronchitis bacterial 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bronchitis viral 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Bronchopneumonia 2/10744 (0%) 14/4904 (0.3%) 17/4881 (0.3%)
    Bronchopulmonary aspergillosis allergic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Campylobacter intestinal infection 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Catheter-site infection 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cellulitis 3/10744 (0%) 19/4904 (0.4%) 17/4881 (0.3%)
    Cellulitis staphylococcal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Central line infection 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cholecystitis infective 0/10744 (0%) 3/4904 (0.1%) 4/4881 (0.1%)
    Chronic sinusitis 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Clostridium difficile colitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cystitis 1/10744 (0%) 7/4904 (0.1%) 2/4881 (0%)
    Dengue fever 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Device-related infection 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Diabetic foot infection 0/10744 (0%) 7/4904 (0.1%) 6/4881 (0.1%)
    Diabetic gangrene 2/10744 (0%) 8/4904 (0.2%) 4/4881 (0.1%)
    Diarrhea infectious 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Diverticulitis 0/10744 (0%) 7/4904 (0.1%) 8/4881 (0.2%)
    Endocarditis 0/10744 (0%) 2/4904 (0%) 4/4881 (0.1%)
    Endocarditis bacterial 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Endocarditis staphylococcal 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Endophthalmitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Entereocolitis viral 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Erysipelas 5/10744 (0%) 23/4904 (0.5%) 14/4881 (0.3%)
    Escherichia sepsis 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Escherichia urinary tract infection 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Eye infection 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Furuncle 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Gallbladder empyema 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gangrene 3/10744 (0%) 3/4904 (0.1%) 5/4881 (0.1%)
    Gastroenteritis 4/10744 (0%) 13/4904 (0.3%) 15/4881 (0.3%)
    Gastroenteritis bacterial 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastroenteritis clostridial 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Gastroenteritis rotavirus 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Gastroenteritis salmonella 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Gastroenteritis viral 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Gingival abscess 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Graft infection 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Groin abscess 1/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Hematoma infection 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Helicobacter infection 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hepatitis A 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hepatitis B 1/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Hepatitis C 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hepatitis viral 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Herpes zoster 2/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Herpes zoster ophthalmic 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Infected sebaceous cyst 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Infected skin ulcer 1/10744 (0%) 7/4904 (0.1%) 2/4881 (0%)
    Infection 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Infective exacerbation of chronic obstructive airways disease 0/10744 (0%) 7/4904 (0.1%) 12/4881 (0.2%)
    Infective tenosynovitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Influenza 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Infusion site infection 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Intervertebral discitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Kidney infection 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Klebsiella sepsis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Labyrinthitis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Laryngitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Liver abscess 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lobar pneumonia 0/10744 (0%) 13/4904 (0.3%) 6/4881 (0.1%)
    Localized infection 0/10744 (0%) 3/4904 (0.1%) 4/4881 (0.1%)
    Lower respiratory tract infection 1/10744 (0%) 4/4904 (0.1%) 10/4881 (0.2%)
    Lung abscess 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Lung infection 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Lung infection pseudomonal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lyme disease 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Lymph node tuberculosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Mastitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Mediastinitis 0/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Meningococcal sepsis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Nasopharyngitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neuroborreliosis 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Oral candidiasis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Orchitis 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Osteomyelitis 3/10744 (0%) 13/4904 (0.3%) 4/4881 (0.1%)
    Otitis media acute 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Otitis media chronic 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Paronychia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Parotitis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Perihepatic abscess 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Perineal abscess 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Perirectal abscess 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Peritonsillar abscess 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Peritonsillitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pharyngeal abscess 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pharyngitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pleurisy viral 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Pneumococcal sepsis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pneumonia 5/10744 (0%) 51/4904 (1%) 59/4881 (1.2%)
    Pneumonia bacterial 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Pneumonia escherichia 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Pneumonia legionella 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Pneumonia pneumococcal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Post-procedural cellulitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post-procedural infection 1/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Postoperative abscess 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Postoperative wound infection 0/10744 (0%) 3/4904 (0.1%) 6/4881 (0.1%)
    Prostatic abscess 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pulmonary sepsis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pulmonary tuberculosis 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Pyelocystitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pyelonephritis 1/10744 (0%) 6/4904 (0.1%) 8/4881 (0.2%)
    Pyelonephritis acute 1/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Pyothorax 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Rash pustular 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Rectal abscess 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Respiratory tract infection 1/10744 (0%) 7/4904 (0.1%) 8/4881 (0.2%)
    Salmonella sepsis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Salmonellosis 3/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Sepsis 0/10744 (0%) 11/4904 (0.2%) 13/4881 (0.3%)
    Septic shock 0/10744 (0%) 9/4904 (0.2%) 6/4881 (0.1%)
    Sinusitis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Sinusitis bacterial 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Skin bacterial infection 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Skin infection 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Staphylococcal infection 1/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Staphylococcal sepsis 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Sternitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Streptococcal sepsis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Subacute endocarditis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Subcutaneous abscess 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Sweat gland infection 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Testicular abscess 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Tonsillitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Tooth abscess 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Toxic shock syndrome 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Tracheitis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Tracheobronchitis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Tuberculosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Upper respiratory tract infection 1/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Urinary tract infection 0/10744 (0%) 16/4904 (0.3%) 23/4881 (0.5%)
    Urinary tract infection bacterial 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Urosepsis 0/10744 (0%) 6/4904 (0.1%) 3/4881 (0.1%)
    Vestibular neuronitis 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Viral infection 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Viral labyrinthitis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Visceral leishmaniasis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vulval cellulitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Wound abscess 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Wound infection 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Wound infection staphylococcal 0/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Accidental needle stick 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Accidental overdose 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Alcohol poisoning 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Anastomotic complication 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ankle fracture 1/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Arterial restenosis 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Ateriovenous fistula thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Asbestosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Brachial plexus injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Brain contusion 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Cardiac pacemaker malfunction 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Cerebral hemorrhage traumatic 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cerebral hyperperfusion syndrome 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Clavicle fracture 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Concussion 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Confusion postoperative 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Contusion 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Coronary artery restenosis 3/10744 (0%) 10/4904 (0.2%) 11/4881 (0.2%)
    Coronary bypass thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Device breakage 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Device dislocation 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Device failure 1/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Device lead damage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Device malfunction 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Device occlusion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Dislocation of joint prosthesis 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Drug administration error 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Drug dispensing error 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Drug toxicity 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Eye injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Face injury 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Fall 0/10744 (0%) 4/4904 (0.1%) 5/4881 (0.1%)
    Femoral neck fracture 1/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Femur fracture 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Fibula fracture 0/10744 (0%) 1/4904 (0%) 4/4881 (0.1%)
    Forearm fracture 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Foreign body trauma 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Fracture displacement 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Fractured sacrum 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastroenteritis radiation 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Gastrointestinal stoma complication 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Graft thrombosis 0/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Hand fracture 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Head injury 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hip fracture 0/10744 (0%) 0/4904 (0%) 6/4881 (0.1%)
    Humerus fracture 0/10744 (0%) 1/4904 (0%) 4/4881 (0.1%)
    Iatrogenic injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Implantable defibrillator malfunction 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    In-stent arterial restenosis 0/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    In-stent coronary artery restenosis 0/10744 (0%) 8/4904 (0.2%) 6/4881 (0.1%)
    Inappropriate device stimulation of tissue 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Incision site complication 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Incisional hernia 0/10744 (0%) 3/4904 (0.1%) 6/4881 (0.1%)
    Incisional hernia, obstructive 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Injury 1/10744 (0%) 6/4904 (0.1%) 4/4881 (0.1%)
    Intervertebral disc injury 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Joint dislocation 1/10744 (0%) 3/4904 (0.1%) 8/4881 (0.2%)
    Joint injury 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Joint sprain 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Keratorhexis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lead dislodgement 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Ligament rupture 1/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Limb injury 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Limb traumatic amputation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lower limb fracture 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Lumbar vertebral fracture 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Medical device complication 0/10744 (0%) 2/4904 (0%) 4/4881 (0.1%)
    Medical device pain 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Meniscus lesion 4/10744 (0%) 5/4904 (0.1%) 6/4881 (0.1%)
    Multiple fractures 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Multiple injuries 1/10744 (0%) 2/4904 (0%) 6/4881 (0.1%)
    Muscle injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Muscle rupture 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Operative hemorrhage 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Overdose 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Patella fracture 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Pelvic fracture 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Periprosthetic osteolysis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post lumbar puncture syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post procedural complication 1/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Post procedural fistula 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Post procedural hematoma 0/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Post procedural hemorrhage 2/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Post procedural myocardial infarction 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post procedural stroke 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post procedural swelling 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Postmastectomy lymphedema syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Postoperative adhesion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Postoperative hernia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Postoperative thoracic procedure complication 2/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Postoperative thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Postoperative wound complication 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Postpericardiotomy syndrome 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Procedural complication 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Procedural hypotension 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Radius fracture 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Rib fracture 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Seroma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Skin laceration 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Skull fractured base 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Soft tissue injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Spinal compression fracture 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Spinal fracture 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Stent occlusion 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Sternal fracture 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Subcutaneous hematoma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Subdural hematoma 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Tendon injury 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Tendon rupture 0/10744 (0%) 2/4904 (0%) 10/4881 (0.2%)
    Therapeutic agent toxicity 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Thoracic vertebral fracture 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Thrombosis in device 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Tibia fracture 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Tongue injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Traumatic amputation 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Traumatic brain injury 0/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Traumatic fracture 4/10744 (0%) 13/4904 (0.3%) 18/4881 (0.4%)
    Traumatic hematoma 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Traumatic lung injury 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Traumatic shock 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Traumatic ulcer 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Upper limb fracture 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Ureteric anastomosis complication 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Urinary retention postoperative 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Vaccination complication 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vascular graft complication 1/10744 (0%) 6/4904 (0.1%) 5/4881 (0.1%)
    Vascular graft occlusion 1/10744 (0%) 5/4904 (0.1%) 3/4881 (0.1%)
    Vascular pseudoaneurysm 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Wound 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Wound dehiscence 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Wound evisceration 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Wound hemorrhage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Wound necrosis 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Wrist fracture 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Investigations
    Angiogram 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Anticoagulation drug level above therapeutic 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Arteriogram coronary 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Arteriogram renal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Blood creatinine increased 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Blood glucose increased 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Blood iron decreased 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Blood potassium decreased 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Body temperature increased 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Cardiac stress test abnormal 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Catheterization cardiac 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Coagulation time prolonged 0/10744 (0%) 1/4904 (0%) 5/4881 (0.1%)
    Colonoscopy 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Diagnostic procedure 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ejection fraction decreased 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hemoglobin decreased 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Heart rate irregular 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hepatic enzyme increased 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    International normalized ratio increased 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Investigation 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Laboratory test abnormal 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Medical observation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Platelet count decreased 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Renal function test abnormal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Scan myocardial perfusion abnormal 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Urine output decreased 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Weight decreased 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Weight increased 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    X-ray abnormal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Diabetes mellitus 3/10744 (0%) 30/4904 (0.6%) 28/4881 (0.6%)
    Diabetes mellitus inadequate control 4/10744 (0%) 67/4904 (1.4%) 50/4881 (1%)
    Diabetes with hyperosmolarity 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Diabetic foot 3/10744 (0%) 17/4904 (0.3%) 15/4881 (0.3%)
    Diabetic ketoacidosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Glucose tolerance impaired 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gout 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Hyperglycemia 0/10744 (0%) 6/4904 (0.1%) 13/4881 (0.3%)
    Hyperkalemia 3/10744 (0%) 6/4904 (0.1%) 5/4881 (0.1%)
    Hyperphagia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypertriglyceridemia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypocalcemia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypoglycemia 1/10744 (0%) 17/4904 (0.3%) 15/4881 (0.3%)
    Hypokalemia 1/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Hyponatremia 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypovolemia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Insulin-requiring type 2 diabetes mellitus 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Lactic acidosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Metabolic acidosis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Metabolic disorder 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Neuroglycopenia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Obesity 0/10744 (0%) 4/4904 (0.1%) 5/4881 (0.1%)
    Type 2 diabetes mellitus 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Weight loss poor 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cervical spinal stenosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Facet joint syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Fibromyalgia 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Arthritis 0/10744 (0%) 7/4904 (0.1%) 10/4881 (0.2%)
    Arthrofibrosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Arthropathy 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Back pain 0/10744 (0%) 9/4904 (0.2%) 13/4881 (0.3%)
    Bone pain 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bunion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bursitis 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Chondrocalcinosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Chondrocalcinosis pyrophosphate 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Chrondopathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Costochondritis 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Dupuytren's contracture 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Exostosis 1/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Foot deformity 1/10744 (0%) 5/4904 (0.1%) 6/4881 (0.1%)
    Gouty arthritis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gouty tophus 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hand deformity 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Intervertebral disc degeneration 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Intervertebral disc disorder 1/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Intervertebral disc protrusion 2/10744 (0%) 15/4904 (0.3%) 15/4881 (0.3%)
    Intervertebral disc space narrowing 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Joint contracture 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Joint effusion 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Joint swelling 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Knee deformity 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Ligament disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lumbar spinal stenosis 0/10744 (0%) 9/4904 (0.2%) 12/4881 (0.2%)
    Metatarsalgia 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Mobility decreased 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Monarthritis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Muscle hemorrhage 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Muscular weakness 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Musculoskeletal chest pain 3/10744 (0%) 6/4904 (0.1%) 14/4881 (0.3%)
    Musculoskeletal discomfort 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Musculoskeletal pain 1/10744 (0%) 8/4904 (0.2%) 11/4881 (0.2%)
    Myalgia 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Myalgia intercostal 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Myositis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Neck pain 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Neuropathic arthropathy 1/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Osteitis 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Osteoarthritis 9/10744 (0.1%) 107/4904 (2.2%) 88/4881 (1.8%)
    Osteochondrosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Osteonecrosis 0/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Osteoporosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Osteoporotic fracture 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pain in extremity 0/10744 (0%) 6/4904 (0.1%) 1/4881 (0%)
    Pain in jaw 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Patellofemoral pain syndrome 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pathological fracture 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Periarthritis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Polyarthritis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Polymyalgia rheumatica 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pseudarthrosis 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Psoriatic arthropathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Rhabdomyolysis 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Rheumatoid arthritis 0/10744 (0%) 5/4904 (0.1%) 1/4881 (0%)
    Rotator cuff syndrome 0/10744 (0%) 8/4904 (0.2%) 8/4881 (0.2%)
    Scleroderma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Senile ankylosing vertebral hyperostosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Spinal column stenosis 0/10744 (0%) 6/4904 (0.1%) 6/4881 (0.1%)
    Spinal disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Spinal osteoarthritis 1/10744 (0%) 6/4904 (0.1%) 12/4881 (0.2%)
    Spondylolisthesis 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Synovial cyst 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Synovitis 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Tendinous contracture 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Tendon calcification 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Tendonitis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Tenosynovitis stenosans 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Trigger finger 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acoustic neuroma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Acute lymphocytic leukemia 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Acute myeloid leukemia 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Adenocarcinoma pancreas 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Adrenal adenoma 0/10744 (0%) 0/4904 (0%) 4/4881 (0.1%)
    Anal cancer 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Astrocytoma malignant 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    B-cell lymphoma 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Basal cell carcinoma 0/10744 (0%) 2/4904 (0%) 4/4881 (0.1%)
    Basosquamous carcinoma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Benign anorectal neoplasm 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Benign breast neoplasm 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Benign colonic neoplasm 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Benign lung neoplasm 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Benign neoplasm of bladder 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Benign renal neoplasm 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Benign salivary gland neoplasm 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Bile duct cancer 0/10744 (0%) 0/4904 (0%) 4/4881 (0.1%)
    Bladder adenocarcinoma stage unspecified 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bladder cancer 1/10744 (0%) 7/4904 (0.1%) 6/4881 (0.1%)
    Bladder cancer recurrent 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Bladder cancer stage 0, with cancer in situ 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder cancer stage II 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder cancer stage III 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder neoplasm 1/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Bladder papilloma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bladder transitional cell carcinoma 1/10744 (0%) 12/4904 (0.2%) 4/4881 (0.1%)
    Bladder transitional cell carcinoma recurrent 1/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Bladder transitional cell carcinoma stage II 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder transitional cell carcinoma stage IV 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bowen's disease 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Breast cancer 0/10744 (0%) 20/4904 (0.4%) 15/4881 (0.3%)
    Breast cancer metastatic 0/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Breast cancer recurrent 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Breast cancer stage I 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Breast cancer stage II 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Breast cancer stage III 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Breast cancer stage IV 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Breast fibroma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bronchial carcinoma 0/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Bronchioalveolar carcinoma 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Cervix carcinoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Chloroma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cholesteatoma 1/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Chronic lymphocytic leukemia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Colon adenoma 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Colon cancer 0/10744 (0%) 11/4904 (0.2%) 10/4881 (0.2%)
    Colon cancer metastatic 0/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Colon cancer stage 0 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Colon cancer stage III 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Colorectal cancer 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Colorectal cancer metastatic 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Diffuse large B-cell lymphoma 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Endometrial cancer 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Endometrial cancer metastatic 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Endometrial cancer stage I 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Follicle center lymphoma, follicular grade I, II, III 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gallbladder cancer metastatic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gammopathy 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Gastric cancer 1/10744 (0%) 6/4904 (0.1%) 3/4881 (0.1%)
    Gastrointestinal carcinoma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Glioblastoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Glioblastoma multiforme 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Head and neck cancer 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hepatic cancer metastatic 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Hepatic neoplasm 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hepatic neoplasm malignant 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hodgkin's disease 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Intraductal papilloma of breast 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Laryngeal cancer 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Leiomyoma 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Leiomyosarcoma metastatic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lentigo maligna stage unspecified 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lip and/or oral cavity cancer 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lip neoplasm malignant stage unspecified 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Lipoma 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Lung adenocarcinoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lung adenocarcinoma metastatic 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Lung adenocarcinoma stage II 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lung cancer metastatic 2/10744 (0%) 9/4904 (0.2%) 4/4881 (0.1%)
    Lung neoplasm 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Lung neoplasm malignant 2/10744 (0%) 5/4904 (0.1%) 8/4881 (0.2%)
    Lung squamous cell carcinoma stage unspecified 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Lymphoma 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Malignant melanoma 1/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Malignant neoplasm of renal pelvis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Malignant neoplasm of uterine adnexa 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Malignant peritoneal neoplasm 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Malignant pleural effusion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Meningioma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Meningioma benign 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Mesothelioma malignant 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Metastases to bladder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metastases to bone marrow 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metastases to liver 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metastasis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metastatic bronchial carcinoma 1/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Metastatic carcinoma of the bladder 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Metastatic gastric cancer 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Metastatic malignant melanoma 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Metastatic neoplasm 0/10744 (0%) 3/4904 (0.1%) 6/4881 (0.1%)
    Metastatic renal cell carcinoma 0/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Metastatic uterine cancer 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Multiple myeloma 0/10744 (0%) 6/4904 (0.1%) 2/4881 (0%)
    Mycosis fungoides 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Myelodysplastic syndrome 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Neoplasm malignant 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Neoplasm of appendix 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neoplasm prostate 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Neurilemmoma malignant 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neuroectodermal neoplasm 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neuroma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Non-Hodgkin's lymphoma 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Non-Hodgkin's lymphoma stage IV 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Non-small cell lung cancer metastatic 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Non-small cell lung cancer stage IV 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Esophageal carcinoma 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Esophageal squamous cell carcinoma metastatic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Oligodendroglioma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Oral papilloma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Ovarian cancer 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Ovarian cancer metastatic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ovarian granulosa-theca cell tumor 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pancoast's tumor 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pancreatic carcinoma 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Pancreatic carcinoma metastatic 1/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Pancreatic neoplasm 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Parathyroid tumor benign 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Pituitary tumor benign 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Plasmacytoma 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Porocarcinoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Prostate cancer 3/10744 (0%) 26/4904 (0.5%) 20/4881 (0.4%)
    Prostate cancer metastatic 0/10744 (0%) 7/4904 (0.1%) 4/4881 (0.1%)
    Prostate cancer recurrent 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Prostate cancer stage I 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Prostate cancer stage II 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Prostatic adenoma 1/10744 (0%) 6/4904 (0.1%) 5/4881 (0.1%)
    Rectal adenoma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Rectal cancer 0/10744 (0%) 6/4904 (0.1%) 5/4881 (0.1%)
    Rectal cancer metastatic 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Rectosigmoid cancer 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Renal cancer 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Renal cancer metastatic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal cancer stage III 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal cell carcinoma 1/10744 (0%) 2/4904 (0%) 4/4881 (0.1%)
    Renal cell carcinoma stage I 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal neoplasm 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Rhabdomyoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Salivary gland adenoma 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Salivary gland cancer 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Sarcoma 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Sarcoma metastatic 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Skin cancer 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Small cell lung cancer metastatic 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Small cell lung cancer stage unspecified 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Spinal hemangioma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Squamous cell carcinoma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Squamous cell carcinoma of skin 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Superficial spreading melanoma stage IV 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Teratoma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Thyroid adenoma 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Thyroid neoplasm 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Tonsil cancer 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Transitional cell carcinoma 0/10744 (0%) 5/4904 (0.1%) 0/4881 (0%)
    Ureteric cancer 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ureteric cancer metastatic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Uterine cancer 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Uterine leiomyoma 0/10744 (0%) 3/4904 (0.1%) 0/4881 (0%)
    Vulval cancer metastatic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Nervous system disorders
    Amnesia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Apallic syndrome 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Basal ganglia hemorrhage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Basilar artery stenosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Brain injury 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Brain stem hemorrhage 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Brain stem infarction 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Brain stem stroke 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Carotid arteriosclerosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Carotid artery occlusion 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Carotid artery stenosis 2/10744 (0%) 30/4904 (0.6%) 32/4881 (0.7%)
    Carotid sinus syndrome 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Carpal tunnel syndrome 2/10744 (0%) 9/4904 (0.2%) 6/4881 (0.1%)
    Central nervous system lesion 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cerebellar infarction 0/10744 (0%) 1/4904 (0%) 3/4881 (0.1%)
    Cerebellar ischemia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cerebellar syndrome 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Cerebral artery embolism 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cerebral artery stenosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cerebral cyst 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cerebral hematoma 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Cerebral hemorrhage 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Cerebral infarction 2/10744 (0%) 15/4904 (0.3%) 12/4881 (0.2%)
    Cerebral ischemia 0/10744 (0%) 3/4904 (0.1%) 7/4881 (0.1%)
    Cerebral thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cerebrovascular accident 8/10744 (0.1%) 46/4904 (0.9%) 44/4881 (0.9%)
    Cerebrovascular insufficiency 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cervical myelopathy 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Cervicobrachial syndrome 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Cluster headache 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cognitive disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Coma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Complicated migraine 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cubital tunnel syndrome 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Dementia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Dementia Alzheimer's type 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diabetic encephalopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diabetic neuropathy 1/10744 (0%) 6/4904 (0.1%) 8/4881 (0.2%)
    Dizziness 1/10744 (0%) 2/4904 (0%) 6/4881 (0.1%)
    Dysaesthesia 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Dysarthria 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Dysstasia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Embolic stroke 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Encephalopathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Epidural lipomatosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Epilepsy 1/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Facial palsy 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Facial paresis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hemorrhage intracranial 1/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Hemorrhagic stroke 2/10744 (0%) 6/4904 (0.1%) 3/4881 (0.1%)
    Hemorrhagic transformation stroke 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Head titubation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Headache 2/10744 (0%) 4/4904 (0.1%) 6/4881 (0.1%)
    Hemiparesis 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Hepatic encephalopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hypertensive encephalopathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypoglycemic coma 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypoxic encephalopathy 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    IIIrd nerve paresis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Incoherent 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Intercostal neuralgia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Intracranial aneurysm 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Intracranial hematoma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Ischemic cerebral infarction 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Ischemic stroke 2/10744 (0%) 42/4904 (0.9%) 22/4881 (0.5%)
    IVth nerve paresis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Lacunar infarction 0/10744 (0%) 1/4904 (0%) 6/4881 (0.1%)
    Lethargy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Loss of consciousness 0/10744 (0%) 7/4904 (0.1%) 6/4881 (0.1%)
    Lumbar radiculopathy 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Meralgia paraesthetica 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metabolic encephalopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Migraine 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Migraine with aura 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Myasthenia gravis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Myelitis transverse 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Myelopathy 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Nerve compression 1/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Neuralgia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neuropathy peripheral 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Paraesthesia 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Paralysis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Parkinson's disease 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Parkinsonism 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Polyneuropathy 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Post-herpetic neuralgia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post-traumatic epilepsy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Presyncope 0/10744 (0%) 7/4904 (0.1%) 7/4881 (0.1%)
    Pseudoradicular syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Radial nerve palsy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Radicular pain 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Radicular syndrome 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Radiculopathy 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Reversible ischemic neurological deficit 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Sciatica 1/10744 (0%) 8/4904 (0.2%) 4/4881 (0.1%)
    Somnolence 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Spinal claudication 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Spinal cord infarction 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Spondylitic myelopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Subarachnoid hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Syncope 2/10744 (0%) 19/4904 (0.4%) 21/4881 (0.4%)
    Thalamic infarction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Transient global amnesia 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Transient ischemic attack 3/10744 (0%) 34/4904 (0.7%) 36/4881 (0.7%)
    Tremor 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Trigeminal neuralgia 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Vascular dementia 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Vascular encephalopathy 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Vertebral artery occlusion 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vertebral artery stenosis 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Vertebrobasilar insufficiency 2/10744 (0%) 5/4904 (0.1%) 8/4881 (0.2%)
    Vertigo CNS origin 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    VIIth nerve paralysis 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    VIth nerve paralysis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Psychiatric disorders
    Abnormal behavior 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Acute psychosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Adjustment disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Alcoholism 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Anxiety 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bereavement reaction 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Completed suicide 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Confusional state 0/10744 (0%) 5/4904 (0.1%) 3/4881 (0.1%)
    Conversion disorder 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Delirium 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Depression 0/10744 (0%) 3/4904 (0.1%) 10/4881 (0.2%)
    Hallucination, visual 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hypochondriasis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Mood disorder due to a general medical condition 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Personality disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post-traumatic stress disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Psychotic disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Schizoaffective disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Schizophreniform disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Suicide attempt 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal and urinary disorders
    Acute prerenal failure 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Azotemia 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Bladder neck obstruction 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bladder neck sclerosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder obstruction 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Bladder prolapse 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Bladder stenosis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bladder tamponade 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Calculus bladder 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Calculus ureteric 0/10744 (0%) 6/4904 (0.1%) 2/4881 (0%)
    Calculus urethral 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Calculus urinary 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Cystitis hemorrhagic 1/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Diabetic nephropathy 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Hematuria 1/10744 (0%) 6/4904 (0.1%) 4/4881 (0.1%)
    Hydronephrosis 0/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Nephrolithiasis 2/10744 (0%) 13/4904 (0.3%) 11/4881 (0.2%)
    Nephropathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Nephropathy toxic 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Nephrotic syndrome 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Obstructive uropathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pollakiuria 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pyuria 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Renal artery arteriosclerosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Renal artery stenosis 0/10744 (0%) 4/4904 (0.1%) 6/4881 (0.1%)
    Renal artery thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Renal colic 0/10744 (0%) 5/4904 (0.1%) 2/4881 (0%)
    Renal cyst 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal failure 3/10744 (0%) 17/4904 (0.3%) 18/4881 (0.4%)
    Renal failure acute 5/10744 (0%) 18/4904 (0.4%) 15/4881 (0.3%)
    Renal failure chronic 0/10744 (0%) 9/4904 (0.2%) 11/4881 (0.2%)
    Renal hypertension 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Renal impairment 0/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Renal tubular necrosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Stress urinary incontinence 0/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Tubulointerstitial nephritis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Ureteric obstruction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Ureteric stenosis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Urethral caruncle 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Urethral hemorrhage 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Urethral meatus stenosis 0/10744 (0%) 5/4904 (0.1%) 0/4881 (0%)
    Urethral stenosis 1/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Urinary bladder hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Urinary bladder polyp 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Urinary incontinence 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Urinary retention 2/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Urinary tract obstruction 2/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Reproductive system and breast disorders
    Acquired hydrocele 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Adenomyosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Balanitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Benign prostatic hyperplasia 8/10744 (0.1%) 39/4904 (0.8%) 30/4881 (0.6%)
    Breast hyperplasia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Breast mass 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Cervical dysplasia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cervical polyp 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Colpocele 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Cystocele 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Endometrial hyperplasia 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Endometrial hypertrophy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Epididymal cyst 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Erectile dysfunction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Fibrocystic breast disease 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Genital prolapse 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Gynecomastia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Metrorrhagia 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Ovarian cyst 1/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Ovarian cyst torsion 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Posthitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Prostatism 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Prostatitis 1/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Prostatomegaly 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Rectocele 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Scrotal cyst 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Testicular swelling 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Uterine polyp 1/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Uterine prolapse 1/10744 (0%) 3/4904 (0.1%) 5/4881 (0.1%)
    Uterovaginal prolapse 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vaginal hemorrhage 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Vaginal prolapse 1/10744 (0%) 0/4904 (0%) 3/4881 (0.1%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary edema 1/10744 (0%) 7/4904 (0.1%) 9/4881 (0.2%)
    Acute respiratory failure 0/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Aspiration 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Asthma 0/10744 (0%) 12/4904 (0.2%) 7/4881 (0.1%)
    Atelectasis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Brain hypoxia 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Bronchial dysplasia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Bronchitis chronic 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Bronchospasm 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Choking 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Chronic obstructive pulmonary disease 6/10744 (0.1%) 17/4904 (0.3%) 21/4881 (0.4%)
    Chronic respiratory failure 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Cough 1/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Dyspnea 2/10744 (0%) 18/4904 (0.4%) 18/4881 (0.4%)
    Dyspnea exertional 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Emphysema 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Epistaxis 1/10744 (0%) 5/4904 (0.1%) 3/4881 (0.1%)
    Foreign body aspiration 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hemoptysis 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Hemothorax 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Hypoventilation 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hypoxia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Interstitial lung disease 0/10744 (0%) 2/4904 (0%) 4/4881 (0.1%)
    Laryngeal granuloma 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Nasal polyps 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Nasal septum deviation 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Nasal septum perforation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Nasal turbinate hypertrophy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Obstructive airways disorder 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Organizing pneumonia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pickwickian syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pleural effusion 0/10744 (0%) 5/4904 (0.1%) 7/4881 (0.1%)
    Pleurisy 0/10744 (0%) 1/4904 (0%) 4/4881 (0.1%)
    Pleuritic pain 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Pneumonia aspiration 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Pneumothorax 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Productive cough 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Pulmonary arterial hypertension 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pulmonary artery thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Pulmonary congestion 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Pulmonary embolism 1/10744 (0%) 15/4904 (0.3%) 11/4881 (0.2%)
    Pulmonary fibrosis 0/10744 (0%) 4/4904 (0.1%) 0/4881 (0%)
    Pulmonary hypertension 0/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Pulmonary edema 1/10744 (0%) 15/4904 (0.3%) 13/4881 (0.3%)
    Respiratory arrest 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Respiratory disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Respiratory failure 0/10744 (0%) 1/4904 (0%) 9/4881 (0.2%)
    Restrictive pulmonary disease 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Sleep apnea syndrome 3/10744 (0%) 14/4904 (0.3%) 14/4881 (0.3%)
    Snoring 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Upper airway obstruction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vocal cord inflammation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Skin and subcutaneous tissue disorders
    Angioedema 0/10744 (0%) 1/4904 (0%) 4/4881 (0.1%)
    Cold sweat 0/10744 (0%) 2/4904 (0%) 3/4881 (0.1%)
    Decubitus ulcer 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Dermatitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Dermatitis allergic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diabetic bullosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diabetic neuropathic ulcer 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Diabetic ulcer 1/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Drug eruption 1/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Dry gangrene 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Eczema 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Eczema asteatotic 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Erythema 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Erythema nodosum 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hidradenitis 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hirsutism 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hyperhidrosis 0/10744 (0%) 3/4904 (0.1%) 4/4881 (0.1%)
    Hypoaesthesia facial 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Leukocytoclastic vasculitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Lichen sclerosis 0/10744 (0%) 2/4904 (0%) 0/4881 (0%)
    Necrobiosis lipoidica diabeticorum 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Neuropathic ulcer 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Psoriasis 2/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Pyoderma gangrenosum 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Scar pain 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Sebaceous hyperplasia 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Skin fissures 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Skin ulcer 0/10744 (0%) 5/4904 (0.1%) 5/4881 (0.1%)
    Social circumstances
    Activities of daily living impaired 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Family stress 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Social stay hospitalization 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Surgical and medical procedures
    Cardiac pacemaker battery replacement 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Cardiac pacemaker replacement 0/10744 (0%) 3/4904 (0.1%) 3/4881 (0.1%)
    Cholecystectomy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Coronary artery bypass 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Diabetes mellitus management 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Drug therapy changed 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Gastric banding 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hip arthroplasty 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hysterectomy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Implantable defibrillator replacement 0/10744 (0%) 3/4904 (0.1%) 1/4881 (0%)
    Intra-uterine contraceptive device removal 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Liposuction 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Medical device change 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Rehabilitation therapy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Therapeutic procedure 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Vascular disorders
    Accelerated hypertension 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Angiodysplasia 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Aortic aneurysm 1/10744 (0%) 12/4904 (0.2%) 13/4881 (0.3%)
    Aortic aneurysm rupture 0/10744 (0%) 1/4904 (0%) 5/4881 (0.1%)
    Aortic arteriosclerosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Aortic dilatation 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Aortic dissection 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Aortic rupture 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Aortic stenosis 0/10744 (0%) 7/4904 (0.1%) 3/4881 (0.1%)
    Arterial disorder 0/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Arterial insufficiency 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Arterial occlusive disease 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Arterial rupture 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Arterial stenosis 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Arterial stenosis limb 0/10744 (0%) 6/4904 (0.1%) 6/4881 (0.1%)
    Arterial thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Arterial thrombosis limb 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Arteriosclerosis 0/10744 (0%) 4/4904 (0.1%) 2/4881 (0%)
    Arteriosclerosis obliterans 0/10744 (0%) 6/4904 (0.1%) 2/4881 (0%)
    Arteriovenous fistula 1/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Arteritis 1/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Circulatory collapse 2/10744 (0%) 0/4904 (0%) 0/4881 (0%)
    Deep vein thrombosis 0/10744 (0%) 13/4904 (0.3%) 15/4881 (0.3%)
    Diabetic microangiopathy 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Diabetic vascular disorder 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Embolism 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Exsanguination 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Extremity necrosis 1/10744 (0%) 3/4904 (0.1%) 2/4881 (0%)
    Femoral arterial stenosis 2/10744 (0%) 18/4904 (0.4%) 13/4881 (0.3%)
    Femoral artery aneurysm 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Femoral artery occlusion 0/10744 (0%) 10/4904 (0.2%) 8/4881 (0.2%)
    Hematoma 0/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Hemorrhage 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Hot flush 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypertension 2/10744 (0%) 17/4904 (0.3%) 26/4881 (0.5%)
    Hypertensive crisis 0/10744 (0%) 5/4904 (0.1%) 10/4881 (0.2%)
    Hypertensive emergency 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Hypotension 1/10744 (0%) 2/4904 (0%) 5/4881 (0.1%)
    Iliac artery occlusion 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Iliac artery stenosis 0/10744 (0%) 6/4904 (0.1%) 3/4881 (0.1%)
    Intermittent claudication 2/10744 (0%) 4/4904 (0.1%) 1/4881 (0%)
    Lymphedema 0/10744 (0%) 2/4904 (0%) 2/4881 (0%)
    Macroangiopathy 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Orthostatic hypotension 0/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Pallor 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Peripheral arterial occlusive disease 3/10744 (0%) 52/4904 (1.1%) 39/4881 (0.8%)
    Peripheral artery aneurysm 1/10744 (0%) 1/4904 (0%) 6/4881 (0.1%)
    Peripheral embolism 0/10744 (0%) 4/4904 (0.1%) 4/4881 (0.1%)
    Peripheral ischemia 1/10744 (0%) 16/4904 (0.3%) 14/4881 (0.3%)
    Peripheral vascular disorder 0/10744 (0%) 12/4904 (0.2%) 11/4881 (0.2%)
    Phlebitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Phlebitis superficial 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Post thrombotic syndrome 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Shock 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Shock hemorrhagic 1/10744 (0%) 4/4904 (0.1%) 3/4881 (0.1%)
    Subclavian artery stenosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Subclavian artery thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Subclavian steal syndrome 1/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Subclavian vein thrombosis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Temporal arteritis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Thromboangiitis obliterans 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Thrombophlebitis 0/10744 (0%) 2/4904 (0%) 1/4881 (0%)
    Thrombophlebitis superficial 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Thrombosis 0/10744 (0%) 0/4904 (0%) 2/4881 (0%)
    Varicophlebitis 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Varicose ulceration 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Varicose vein 1/10744 (0%) 14/4904 (0.3%) 2/4881 (0%)
    Vascular rupture 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vascular shunt 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vascular stenosis 0/10744 (0%) 1/4904 (0%) 1/4881 (0%)
    Vasculitis 0/10744 (0%) 0/4904 (0%) 1/4881 (0%)
    Vasculitis necrotizing 0/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Venous insufficiency 0/10744 (0%) 8/4904 (0.2%) 3/4881 (0.1%)
    Venous thrombosis 1/10744 (0%) 1/4904 (0%) 0/4881 (0%)
    Venous thrombosis limb 0/10744 (0%) 1/4904 (0%) 2/4881 (0%)
    Other (Not Including Serious) Adverse Events
    Lead-in Period Sibutramine Randomized Sibutramine Randomized Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)

    Limitations/Caveats

    Most subjects not indicated for sibutramine (sbt) due to CV disease. Long-term sbt use (6 yrs) regardless of weight loss, is inconsistent with label (limits use to 1-2 yrs & 5% weight loss). Trial lacked true placebo; all received Lead-in Period sbt.

    More Information

    Certain Agreements

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

    Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.

    Results Point of Contact

    Name/Title Global Medical Services
    Organization Abbott
    Phone 800-633-9110
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00234832
    Other Study ID Numbers:
    • M01-392
    First Posted:
    Oct 10, 2005
    Last Update Posted:
    May 11, 2010
    Last Verified:
    May 1, 2010