RECORD: Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00379769
First received: September 21, 2006
Last updated: December 13, 2013
Last verified: December 2013
Results First Received: August 24, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Rosiglitazone
Drug: Sulfonylurea
Drug: Metformin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The RECORD study ran from April 2001 through December 2008. Results are presented in the non-re-adjudicated outcome measures (OMs). An independent patient-level re-adjudication of mortality, non-fatal myocardial infarction, and non-fatal stroke began on January 2011 and ran through March 2012. The results are presented in the re-adjudicated OMs.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The RECORD observational follow-up (OFU) started at the end of the RECORD study and ran through December 2012. OFU was designed to collect cancer and bone fracture data. Participants were not provided with study medication in the OFU. Data are presented for the entire study (RECORD + OBF) and for OFU alone in the observational OMs.

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator’s discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Participant Flow for 2 periods

Period 1:   Main Study
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
STARTED     1117     1105     1103     1122     0     0  
COMPLETED     939     906     896     892     0     0  
NOT COMPLETED     178     199     207     230     0     0  
Death                 57                 67                 54                 72                 0                 0  
Adverse Event                 5                 8                 10                 11                 0                 0  
Lost to Follow-up                 29                 29                 25                 26                 0                 0  
Withdrawal by Subject                 46                 56                 72                 70                 0                 0  
Moved to survival status follow-up only                 27                 25                 32                 36                 0                 0  
Participant moved                 3                 2                 3                 3                 0                 0  
Poor compliance                 3                 2                 2                 1                 0                 0  
Prohibited glucose lowering medication                 0                 3                 0                 1                 0                 0  
Site closed                 4                 4                 4                 8                 0                 0  
Entry criteria violation                 0                 0                 1                 1                 0                 0  
Participant did not take study drug                 0                 0                 1                 0                 0                 0  
Physician Decision                 2                 2                 1                 1                 0                 0  
Participant completed study at visit 27                 1                 0                 0                 0                 0                 0  
Personal reasons                 1                 0                 0                 0                 0                 0  
Risk of heart failure                 0                 1                 0                 0                 0                 0  
Investigator refused to log temperature                 0                 0                 1                 0                 0                 0  
Reason unspecified                 0                 0                 1                 0                 0                 0  

Period 2:   Observational Follow-up
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
STARTED     0     0     0     0     1280 [1]   1250 [2]
COMPLETED     0     0     0     0     1131     1102  
NOT COMPLETED     0     0     0     0     149     148  
Death                 0                 0                 0                 0                 78                 70  
Adverse Event                 0                 0                 0                 0                 1                 0  
Lost to Follow-up                 0                 0                 0                 0                 25                 27  
Withdrawal by Subject                 0                 0                 0                 0                 12                 12  
Entered into Another Clinical Trial                 0                 0                 0                 0                 18                 22  
Physician Decision                 0                 0                 0                 0                 8                 8  
Site Closed Early                 0                 0                 0                 0                 6                 7  
Participant Moved                 0                 0                 0                 0                 0                 1  
Unknown; Reason Not Provided                 0                 0                 0                 0                 1                 1  
[1] 665 from “RSG in Addition to Background MET” arm; 615 from “RGS in Addition to Background SU” arm.
[2] 647 from “SU in Addition to Background MET” arm; 603 from “MET in Addition to Background SU” arm.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Total Total of all reporting groups

Baseline Measures
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Total  
Number of Participants  
[units: participants]
  1117     1105     1103     1122     4447  
Age  
[units: years]
Mean ± Standard Deviation
  57.0  ± 8.02     57.2  ± 8.14     59.8  ± 8.26     59.7  ± 8.23     58.4  ± 8.27  
Gender  
[units: participants]
         
Female     516     521     562     554     2153  
Male     601     584     541     568     2294  
Race/Ethnicity, Customized  
[units: participants]
         
White     1105     1087     1095     1112     4399  
Black     3     6     2     3     14  
Oriental     4     2     5     7     18  
Aboriginal     1     0     0     0     1  
African     1     0     0     0     1  
Asian     1     2     1     0     4  
Egyptian     1     0     0     0     1  
Gipsy     1     0     0     0     1  
Indian     0     1     0     0     1  
Maori     0     1     0     0     1  
Middle East Hible     0     1     0     0     1  
Pacific Islander     0     1     0     0     1  
Polynesian     0     1     0     0     1  
Sri Lankan     0     2     0     0     2  
Tahitian     0     1     0     0     1  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

2.  Primary:   Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

3.  Primary:   Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

4.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

5.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

6.  Primary:   Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

7.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

8.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

9.  Primary:   Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

10.  Primary:   Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

11.  Secondary:   Number of Participants With Cardiovascular Events and All-cause Deaths   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

12.  Secondary:   Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

13.  Secondary:   Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

14.  Secondary:   Number of Participants With CV/Microvascular Events   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

15.  Secondary:   Number of Participants With Glycaemic Failure Events   [ Time Frame: Baseline through to end of randomised dual therapy ]

16.  Secondary:   Number of Participants With Addition of Third Oral Agent/Switch to Insulin   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

17.  Secondary:   The Number of Participants Starting Insulin at Any Time During the Study   [ Time Frame: Baseline through End of Study (up to 7.5 years) ]

18.  Secondary:   Model Adjusted Change From Baseline in HbA1c at Month 60   [ Time Frame: Baseline and Month 60 of randomised dual therapy treatment period ]

19.  Secondary:   Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

20.  Secondary:   Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

21.  Secondary:   Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

22.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

23.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

24.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

25.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment period ]

26.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

27.  Secondary:   Model Adjusted Change From Baseline in Body Weight at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

28.  Secondary:   Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

29.  Secondary:   Model Adjusted Change From Baseline in Waist Circumference at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

30.  Secondary:   Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

31.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

32.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

33.  Secondary:   Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60   [ Time Frame: Baseline to Month 60 of the randomised dual therapy treatment phase ]

34.  Secondary:   Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

35.  Secondary:   Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

36.  Secondary:   Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

37.  Secondary:   Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

38.  Secondary:   Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

39.  Secondary:   Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

40.  Secondary:   Number of Participants With a Bone Fracture Event – Overall and by Gender: Main Study and Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

41.  Secondary:   Number of Participants With a Bone Fracture Event – Overall and by Gender: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

42.  Secondary:   Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

43.  Secondary:   Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

44.  Secondary:   Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

45.  Secondary:   Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

46.  Secondary:   Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

47.  Secondary:   Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

48.  Secondary:   Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

49.  Secondary:   Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

50.  Secondary:   Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

51.  Secondary:   Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined   [ Time Frame: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years) ]

52.  Secondary:   Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]

53.  Secondary:   Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up   [ Time Frame: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years) ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame In the RECORD study (RS), SAEs were collected from BL through End of Study (up to 7.5 years); non-serious AEs were collected only for the randomized treatment period. SAEs were collected from the end of the RS through the end of OFU (up to 4.0 years).
Additional Description The Observational Follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. Other than bone fractures (tabulated in the Outcome Measure Module), no non-serious AEs were collected.

Reporting Groups
  Description
RSG in Addition to Background MET Participants inadequately controlled on background metformin (MET) were randomised to receive rosiglitazone (RSG), in addition to MET. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
SU in Addition to Background MET Participants inadequately controlled on background MET were randomised to receive, in addition to MET, a sulfonylurea (SU) (glibenclamide, gliclazide, or glimepiride). The SU was gradually increased to the maximum permitted dose (glibenclamide 15 mg per day or micronized equivalent of 10.5 mg per day; gliclazide 240 mg per day; glimepiride 4 mg per day) as required to achieve a target HbA1c of less than or equal to 7.0 percent.
RSG in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, RSG. RSG was initiated as a 4 mg once daily dose and was increased to a maximum dose of 8 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
MET in Addition to Background SU Participants inadequately controlled on background SU were randomised to receive, in addition to SU, MET. MET was gradually increased to the maximum permitted dose of 2550 mg per day as required to achieve a target HbA1c of less than or equal to 7.0 percent.
Combined RSG: Observational Follow-up Participants randomized to receive RSG (MET+RSG and SU+RSG) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.
Combined MET/SU: Observational Follow-up Participants randomized to the active control groups (MET+SU and SU+MET) in the main RECORD study. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion.

Serious Adverse Events
    RSG in Addition to Background MET     SU in Addition to Background MET     RSG in Addition to Background SU     MET in Addition to Background SU     Combined RSG: Observational Follow-up     Combined MET/SU: Observational Follow-up  
Total, serious adverse events              
# participants affected / at risk     424/1117 (37.96%)     428/1105 (38.73%)     427/1103 (38.71%)     431/1122 (38.41%)     99/1280 (7.73%)     76/1250 (6.08%)  
Blood and lymphatic system disorders              
Anaemia † 1            
# participants affected / at risk     8/1117 (0.72%)     2/1105 (0.18%)     4/1103 (0.36%)     5/1122 (0.45%)     1/1280 (0.08%)     0/1250 (0.00%)  
Iron Deficiency Anaemia † 1            
# participants affected / at risk     1/1117 (0.09%)     3/1105 (0.27%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hypocoagulable State † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Thrombocytopenia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Idiopathic Thrombocytopenic Purpura † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Autoimmune Thrombocytopenia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Haemolytic Anaemia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac disorders              
Myocardial Infarction † 1            
# participants affected / at risk     25/1117 (2.24%)     22/1105 (1.99%)     29/1103 (2.63%)     23/1122 (2.05%)     0/1280 (0.00%)     1/1250 (0.08%)  
Cardiac Failure Congestive † 1            
# participants affected / at risk     25/1117 (2.24%)     18/1105 (1.63%)     23/1103 (2.09%)     13/1122 (1.16%)     0/1280 (0.00%)     0/1250 (0.00%)  
Angina Pectoris † 1            
# participants affected / at risk     23/1117 (2.06%)     18/1105 (1.63%)     23/1103 (2.09%)     19/1122 (1.69%)     0/1280 (0.00%)     0/1250 (0.00%)  
Angina Unstable † 1            
# participants affected / at risk     16/1117 (1.43%)     20/1105 (1.81%)     21/1103 (1.90%)     18/1122 (1.60%)     0/1280 (0.00%)     0/1250 (0.00%)  
Atrial Fibrillation † 1            
# participants affected / at risk     20/1117 (1.79%)     15/1105 (1.36%)     13/1103 (1.18%)     14/1122 (1.25%)     0/1280 (0.00%)     0/1250 (0.00%)  
Acute Myocardial Infarction † 1            
# participants affected / at risk     12/1117 (1.07%)     6/1105 (0.54%)     11/1103 (1.00%)     19/1122 (1.69%)     1/1280 (0.08%)     1/1250 (0.08%)  
Cardiac Failure † 1            
# participants affected / at risk     16/1117 (1.43%)     1/1105 (0.09%)     13/1103 (1.18%)     8/1122 (0.71%)     0/1280 (0.00%)     0/1250 (0.00%)  
Coronary Artery Disease † 1            
# participants affected / at risk     9/1117 (0.81%)     6/1105 (0.54%)     7/1103 (0.63%)     12/1122 (1.07%)     0/1280 (0.00%)     0/1250 (0.00%)  
Myocardial Ischaemia † 1            
# participants affected / at risk     7/1117 (0.63%)     5/1105 (0.45%)     7/1103 (0.63%)     5/1122 (0.45%)     0/1280 (0.00%)     0/1250 (0.00%)  
Coronary Artery Stenosis † 1            
# participants affected / at risk     4/1117 (0.36%)     8/1105 (0.72%)     5/1103 (0.45%)     7/1122 (0.62%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac Failure Acute † 1            
# participants affected / at risk     3/1117 (0.27%)     2/1105 (0.18%)     3/1103 (0.27%)     3/1122 (0.27%)     1/1280 (0.08%)     0/1250 (0.00%)  
Arrythmia † 1            
# participants affected / at risk     1/1117 (0.09%)     4/1105 (0.36%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bradycardia † 1            
# participants affected / at risk     1/1117 (0.09%)     3/1105 (0.27%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Acute Coronary Syndrome † 1            
# participants affected / at risk     3/1117 (0.27%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Arteriosclerosis Coronary Artery † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Tachycardia † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Atrioventricular Block Complete † 1            
# participants affected / at risk     1/1117 (0.09%)     2/1105 (0.18%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac Arrest † 1            
# participants affected / at risk     1/1117 (0.09%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Aortic Valve Disease † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sick Sinus Syndrome † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Atrial Flutter † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     1/1103 (0.09%)     4/1122 (0.36%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac Disorder † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Silent Myocardial Infarction † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Mitral Valve Incompetence † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Atrial Tachycardia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Atrioventricular Block Second Degree † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac Failure Chronic † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiomegaly † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiovascular disorder † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cor pulmonale † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Left Ventricular Failure † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Mitral Valve Disease † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pericarditis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Right Ventricular Failure † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sinus Bradycardia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Ventricular Arrhythmia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Ventricular Fibrillation † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Congestive Cardiomyopathy † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sinus Tachycardia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     2/1103 (0.18%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Supraventricular Tachycardia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Tachyarrhythmia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Aortic Valve Stenosis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Coronary Artery Occlusion † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Extrasystoles † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pericardial Effusion † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Tachycardia Paroxysmal † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Ventricular Extrasystoles † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Atrioventricular Block † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bradyarrhythmia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac Fibrillation † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiac Flutter † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cardiomyopathy † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Adams-Stokes Syndrome † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hypertensive Cardiomyopathy † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Left Ventricular Hypertrophy † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Myocardial Fibrosis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Supraventricular Extrasystoles † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Tricuspid Valve Incompetence † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Congenital, familial and genetic disorders              
Corneal Dystrophy † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hydrocele † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastrointestinal Angiodysplasia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Ear and labyrinth disorders              
Vertigo † 1            
# participants affected / at risk     3/1117 (0.27%)     4/1105 (0.36%)     6/1103 (0.54%)     5/1122 (0.45%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hypoacusis † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Otosclerosis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sudden Hearing Loss † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Tinnitus † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Vestibular Disorder † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Vestibular Neuronitis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Vertigo Positional † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Endocrine disorders              
Goitre † 1            
# participants affected / at risk     2/1117 (0.18%)     2/1105 (0.18%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hyperthyroidism † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hyperparathyroidism † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hyperparathyroidism Primary † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Parathyroid Gland Enlargement † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Toxic Nodular Goitre † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Adrenal Mass † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Basedow's Disease † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Eye disorders              
Cataract † 1            
# participants affected / at risk     5/1117 (0.45%)     3/1105 (0.27%)     12/1103 (1.09%)     9/1122 (0.80%)     0/1280 (0.00%)     0/1250 (0.00%)  
Retinal Detachment † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Angle Closure Glaucoma † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Maculopathy † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Glaucoma † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cataract Nuclear † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Inflammation of Lacrimal Passage † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Retinal Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Vitreous Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diabetic Retinopathy † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Eye Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Dacryostenosis Acquired † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Exudative Retinopathy † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Macular Degeneration † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Optic Atrophy † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Keratitis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Lens Dislocation † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Retinal Vein Thrombosis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastrointestinal disorders              
Abdominal Pain † 1            
# participants affected / at risk     5/1117 (0.45%)     5/1105 (0.45%)     0/1103 (0.00%)     1/1122 (0.09%)     1/1280 (0.08%)     0/1250 (0.00%)  
Pancreatitis Acute † 1            
# participants affected / at risk     6/1117 (0.54%)     3/1105 (0.27%)     4/1103 (0.36%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastrointestinal Haemorrhage † 1            
# participants affected / at risk     3/1117 (0.27%)     3/1105 (0.27%)     2/1103 (0.18%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastritis † 1            
# participants affected / at risk     3/1117 (0.27%)     2/1105 (0.18%)     3/1103 (0.27%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Rectal haemorrhage † 1            
# participants affected / at risk     2/1117 (0.18%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Constipation † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diarrhoea † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Duodenal ulcer Haemorrhage † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastric Ulcer Haemorrhage † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Umbilical Hernia † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     0/1103 (0.00%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Crohn's Disease † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Haemorrhoids † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Colitis Ulcerative † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Duodenal ulcer † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Dyspepsia † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastric Polyps † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hiatus Hernia † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Inguinal hernia † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pancreatitis † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     3/1103 (0.27%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diverticulum † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Dysphagia † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastric Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intestinal Perforation † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Vomiting † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Abdominal Hernia Obstructive † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Abdominal Pain Upper † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Dental caries † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diverticulum Intestinal † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     4/1122 (0.36%)     0/1280 (0.00%)     0/1250 (0.00%)  
Faeces Discoloured † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastric Dysplasia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastric Ulcer † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastritis Haemorrhagic † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastrointestinal Inflammation † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastrooesophageal Reflux Disease † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Haematochezia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Haemorrhoidal Haemorrhage † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intestinal Fistula † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Melaena † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pancreatic Pseudocyst † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Peritoneal Disorder † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Proctalgia † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Splenic Artery Aneurysm † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Upper Gastrointestinal Haemorrhage † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Abdominal Hernia † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     2/1103 (0.18%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Anal Fistula † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Appendicitis Perforated † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Ascites † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Colonic Fistula † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Colonic Polyp † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diverticular Perforation † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diverticulitis Intestinal Haemorrhagic † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Duodenal Perforation † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Flatulence † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Ileus † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intestinal Obstruction † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Mechanical Ileus † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Nausea † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Reflux Oesophagitis † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Small Intestinal Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pancreatitis Chronic † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastric Ulcer Perforation † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Abdominal Adhesions † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastroduodenitis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pancreatic Cyst † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pancreatitis Necrotising † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Peptic Ulcer Perforation † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Duodenal Fistula † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastroduodenal Ulcer † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intestinal Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pancreatic necrosis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     1/1280 (0.08%)     0/1250 (0.00%)  
Peritonitis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Rectal Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Rectal Polyp † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Salivary Gland Calculus † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Barrett's oesophagus † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Duodenitis Haemorrhagic † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Enterocele † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Enterocolitis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Faecaloma † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastrointestinal Disorder † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Haematemesis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intestinal Polyp † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intra-abdominal haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Oesophagitis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Peptic Ulcer Haemorrhage † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Small Intestinal Obstruction † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
General disorders              
Non-Cardiac Chest Pain † 1            
# participants affected / at risk     14/1117 (1.25%)     12/1105 (1.09%)     5/1103 (0.45%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Death † 1            
# participants affected / at risk     5/1117 (0.45%)     3/1105 (0.27%)     2/1103 (0.18%)     6/1122 (0.53%)     0/1280 (0.00%)     2/1250 (0.16%)  
Pyrexia † 1            
# participants affected / at risk     4/1117 (0.36%)     2/1105 (0.18%)     3/1103 (0.27%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sudden Death † 1            
# participants affected / at risk     1/1117 (0.09%)     3/1105 (0.27%)     4/1103 (0.36%)     4/1122 (0.36%)     0/1280 (0.00%)     1/1250 (0.08%)  
Inflammation † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Multi-Organ Failure † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sudden Cardiac Death † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     2/1103 (0.18%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Chest pain † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     1/1280 (0.08%)     0/1250 (0.00%)  
Gait Disturbance † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hernia Obstructive † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Chest Discomfort † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
General Physical Health Deterioration † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pain † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Drowning † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     2/1122 (0.18%)     1/1280 (0.08%)     0/1250 (0.00%)  
Oedema † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Oedema Peripheral † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Tenderness † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Brain Death † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Dysplasia † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     1/1280 (0.08%)     0/1250 (0.00%)  
Hepatobiliary disorders              
Cholelithiasis † 1            
# participants affected / at risk     15/1117 (1.34%)     13/1105 (1.18%)     9/1103 (0.82%)     10/1122 (0.89%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cholecystitis † 1            
# participants affected / at risk     5/1117 (0.45%)     5/1105 (0.45%)     4/1103 (0.36%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cholecystitis Acute † 1            
# participants affected / at risk     2/1117 (0.18%)     2/1105 (0.18%)     5/1103 (0.45%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Liver Disorder † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Biliary Colic † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     2/1103 (0.18%)     0/1122 (0.00%)     1/1280 (0.08%)     0/1250 (0.00%)  
Cholangitis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cholecystitis Chronic † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatic Failure † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bile Duct Obstruction † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bile Duct Stone † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatic Steatosis † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Jaundice † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Jaundice Cholestatic † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatic Cirrhosis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gallbladder Polyp † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cholestasis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatitis † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatitis Alcoholic † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Post Cholecystectomy Syndrome † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatic lesion † 1            
# participants affected / at risk     0/1117 (0.00%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     1/1250 (0.08%)  
Immune system disorders              
Drug Hypersensitivity † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hypersensitivity † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     3/1103 (0.27%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Anaphylactic Reaction † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Infections and infestations              
Pnuemonia † 1            
# participants affected / at risk     21/1117 (1.88%)     15/1105 (1.36%)     11/1103 (1.00%)     12/1122 (1.07%)     0/1280 (0.00%)     0/1250 (0.00%)  
Erysipelas † 1            
# participants affected / at risk     6/1117 (0.54%)     7/1105 (0.63%)     6/1103 (0.54%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sepsis † 1            
# participants affected / at risk     6/1117 (0.54%)     5/1105 (0.45%)     4/1103 (0.36%)     3/1122 (0.27%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cellulitis † 1            
# participants affected / at risk     4/1117 (0.36%)     6/1105 (0.54%)     3/1103 (0.27%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bronchitis † 1            
# participants affected / at risk     2/1117 (0.18%)     6/1105 (0.54%)     4/1103 (0.36%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pyelonephritis † 1            
# participants affected / at risk     1/1117 (0.09%)     6/1105 (0.54%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Urinary Tract Infection † 1            
# participants affected / at risk     4/1117 (0.36%)     2/1105 (0.18%)     3/1103 (0.27%)     5/1122 (0.45%)     1/1280 (0.08%)     0/1250 (0.00%)  
Lower Respiratory Tract Infection † 1            
# participants affected / at risk     2/1117 (0.18%)     4/1105 (0.36%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bronchopnuemonia † 1            
# participants affected / at risk     1/1117 (0.09%)     5/1105 (0.45%)     4/1103 (0.36%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gangrene † 1            
# participants affected / at risk     0/1117 (0.00%)     4/1105 (0.36%)     3/1103 (0.27%)     4/1122 (0.36%)     0/1280 (0.00%)     0/1250 (0.00%)  
Diverticulitis † 1            
# participants affected / at risk     2/1117 (0.18%)     1/1105 (0.09%)     2/1103 (0.18%)     5/1122 (0.45%)     0/1280 (0.00%)     0/1250 (0.00%)  
Abdominal Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastroenteritis † 1            
# participants affected / at risk     1/1117 (0.09%)     2/1105 (0.18%)     2/1103 (0.18%)     5/1122 (0.45%)     0/1280 (0.00%)     0/1250 (0.00%)  
Post Procedural Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     2/1105 (0.18%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Urosepsis † 1            
# participants affected / at risk     1/1117 (0.09%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Localised Infection † 1            
# participants affected / at risk     0/1117 (0.00%)     3/1105 (0.27%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Postoperative Wound Infection † 1            
# participants affected / at risk     2/1117 (0.18%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Anal Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Orchitis † 1            
# participants affected / at risk     1/1117 (0.09%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pyelonephritis Acute † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     3/1103 (0.27%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Sinusitis † 1            
# participants affected / at risk     0/1117 (0.00%)     2/1105 (0.18%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Abscess Intestinal † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Appendiceal Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Bacterial Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Brochiectasis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Campylobacter Gastroenteritis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cholecystitis Infective † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Encephalitis Viral † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Endocarditis Viral † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Herpes Zoster † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Infective Exacercbatn of Chronic Obstructive Airways Disease † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Infective Thrombosis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Joint Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Laryngitis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Liver Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Mastitis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Myocardiac Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Osteomyelitis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     2/1103 (0.18%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pelvic Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Pharyngitis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Phlebitis Infective † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Retroperitoneal Abscess † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Staphylococcal Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Toxoplasmosis † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Upper Respiratory Tract Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Viral Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     0/1103 (0.00%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Wound Infection † 1            
# participants affected / at risk     1/1117 (0.09%)     0/1105 (0.00%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Appendicitis † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     4/1103 (0.36%)     2/1122 (0.18%)     0/1280 (0.00%)     0/1250 (0.00%)  
Arthritis Bacterial † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Catheter Sepsis † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Conjunctivitis Viral † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Cystitis † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     1/1122 (0.09%)     0/1280 (0.00%)     0/1250 (0.00%)  
Enteritis Infectious † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Gastroenteritis Bacterial † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Groin Abscess † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Hepatitis C † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Herpes Zoster Oticus † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Infection † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     1/1103 (0.09%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Infective Myositis † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Intestinal Gangrene † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Lobar Pneumonia † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     4/1103 (0.36%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Lung Infection † 1            
# participants affected / at risk     0/1117 (0.00%)     1/1105 (0.09%)     0/1103 (0.00%)     0/1122 (0.00%)     0/1280 (0.00%)     0/1250 (0.00%)  
Lyme Disease † 1            
# participants affected / at risk