Safety and Efficacy of Empagliflozin (BI 10773) and Sitagliptin Versus Placebo Over 76 Weeks in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01289990
First received: January 31, 2011
Last updated: July 14, 2014
Last verified: July 2014
Results First Received: May 16, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: BI 10773
Drug: Placebo
Drug: Sitagliptin 100mg

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Empagliflozin 10 mg (Drug Naive)

Patients rolled over from trial 1245.20

Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Drug Naive)

Patients rolled over from trial 1245.20

Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Drug Naive)

Patients rolled over from trial 1245.20

Placebo tablets matching Empagliflozin / Sitagliptin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 25 mg

Sitagliptin 100mg (Drug Naive)

Patients rolled over from trial 1245.20

Sitagliptin once daily

Placebo: Placebo matching Empagliflozin 25 mg

Placebo: Placebo matching Empagliflozin 10 mg

Sitagliptin 100mg: Sitagliptin once daily

Empagliflozin 10 mg (Pioglitazone)

Patients rolled over from trial 1245.19

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Pioglitazone)

Patients rolled over from trial 1245.19

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Pioglitazone)

Patients rolled over from trial 1245.19

Placebo tablets matching Empagliflozin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg (Metformin)

Patients rolled over from trial 1245.23

Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg: Empagliflozin 10 mg once daily

Empagliflozin 25 mg (Metformin)

Patients rolled over from trial 1245.23

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Metformin)

Patients rolled over from trial 1245.23

Placebo tablets matching Empagliflozin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Placebo tablets matching Empagliflozin

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg


Participant Flow:   Overall Study
    Empagliflozin 10 mg (Drug Naive)     Empagliflozin 25 mg (Drug Naive)     Placebo (Drug Naive)     Sitagliptin 100mg (Drug Naive)     Empagliflozin 10 mg (Pioglitazone)     Empagliflozin 25 mg (Pioglitazone)     Placebo (Pioglitazone)     Empagliflozin 10 mg (Metformin)     Empagliflozin 25 mg (Metformin)     Placebo (Metformin)     Empagliflozin 10 mg (Metformin+Sulfonylurea)     Empagliflozin 25 mg (Metformin+Sulfonylurea)     Placebo (Metformin+Sulfonylurea)  
STARTED     224     224     228     223     165     168     166     217     214     207     226     218     225  
COMPLETED     147     143     119     136     93     94     78     162     139     121     150     150     127  
NOT COMPLETED     77     81     109     87     72     74     88     55     75     86     76     68     98  
Death                 0                 0                 0                 1                 2                 1                 0                 0                 0                 0                 0                 1                 0  
Lost to Follow-up                 3                 2                 5                 5                 3                 4                 2                 2                 1                 4                 2                 1                 2  
Withdrawal by Subject                 15                 14                 12                 13                 8                 7                 13                 9                 12                 13                 11                 13                 16  
discontinued in preceding trial                 18                 20                 41                 17                 11                 12                 18                 8                 17                 21                 17                 17                 24  
did not continue in extension                 41                 45                 51                 51                 48                 50                 54                 36                 44                 48                 45                 34                 56  
Not treated                 0                 0                 0                 0                 0                 0                 1                 0                 1                 0                 1                 2                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Full Analysis Set (FAS): which contained all randomised patients who received at least 1 dose of study drug and had a baseline HbA1c assessment, irrespective of participation in the extension trial.

Reporting Groups
  Description
Empagliflozin 10 mg (Drug Naive)

Patients rolled over from trial 1245.20

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Drug Naive)

Patients rolled over from trial 1245.20

Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Sitagliptin

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Drug Naive)

Patients rolled over from trial 1245.20

Placebo tablets matching Empagliflozin / Sitagliptin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 25 mg

Sitagliptin 100 mg (Drug Naive)

Patients rolled over from trial 1245.20

Sitagliptin once daily

Placebo: Placebo matching Empagliflozin 25 mg

Placebo: Placebo matching Empagliflozin 10 mg

Sitagliptin 100 mg: Sitagliptin once daily

Empagliflozin 10 mg (Pioglitazone)

Patients rolled over from trial 1245.19

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Pioglitazone)

Patients rolled over from trial 1245.19

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Pioglitazone)

Patients rolled over from trial 1245.19

Placebo tablets matching Empagliflozin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg (Metformin)

Patients rolled over from trial 1245.23

Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg: Empagliflozin 10 mg once daily

Empagliflozin 25 mg (Metformin)

Patients rolled over from trial 1245.23

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Metformin)

Patients rolled over from trial 1245.23

Placebo tablets matching Empagliflozin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Placebo tablets matching Empagliflozin

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Total Total of all reporting groups

Baseline Measures
    Empagliflozin 10 mg (Drug Naive)     Empagliflozin 25 mg (Drug Naive)     Placebo (Drug Naive)     Sitagliptin 100 mg (Drug Naive)     Empagliflozin 10 mg (Pioglitazone)     Empagliflozin 25 mg (Pioglitazone)     Placebo (Pioglitazone)     Empagliflozin 10 mg (Metformin)     Empagliflozin 25 mg (Metformin)     Placebo (Metformin)     Empagliflozin 10 mg (Metformin+Sulfonylurea)     Empagliflozin 25 mg (Metformin+Sulfonylurea)     Placebo (Metformin+Sulfonylurea)     Total  
Number of Participants  
[units: participants]
  224     224     228     223     165     168     165     217     213     207     225     216     225     2700  
Age  
[units: years]
Mean ± Standard Deviation
  56.2  ± 11.6     53.8  ± 11.6     54.9  ± 10.9     55.1  ± 9.9     54.7  ± 9.9     54.2  ± 8.9     54.6  ± 10.5     55.5  ± 9.9     55.6  ± 10.2     56.0  ± 9.7     57.0  ± 9.2     57.4  ± 9.3     56.9  ± 9.2     55.6  ± 10.2  
Gender  
[units: participants]
                           
Female     82     79     105     82     82     83     92     92     93     91     112     102     113     1208  
Male     142     145     123     141     83     85     73     125     120     116     113     114     112     1492  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Changes From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 52 Weeks of Treatment   [ Time Frame: Baseline and 52 weeks ]

2.  Primary:   Changes From Baseline in HbA1c (%) After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]

3.  Secondary:   HbA1c (%) Changes From Baseline After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]

4.  Secondary:   Systolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment   [ Time Frame: Baseline and 52 weeks ]

5.  Secondary:   Systolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]

6.  Secondary:   Diastolic Blood Pressure: Change From Baseline After 52 Weeks of Treatment   [ Time Frame: Baseline and 52 weeks ]

7.  Secondary:   Diastolic Blood Pressure: Change From Baseline After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]

8.  Secondary:   Body Weight (kg) Change From Baseline After 52 Weeks of Treatment   [ Time Frame: Baseline and 52 weeks ]

9.  Secondary:   Body Weight (kg) Change From Baseline After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]

10.  Secondary:   Waist Circumference (cm) Change From Baseline After 52 Weeks of Treatment   [ Time Frame: Baseline and 52 weeks ]

11.  Secondary:   Waist Circumference (cm) Change From Baseline After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]

12.  Secondary:   Fasting Plasma Glucose Change From Baseline After 52 Weeks of Treatment   [ Time Frame: Baseline and 52 weeks ]

13.  Secondary:   Fasting Plasma Glucose Change From Baseline After 76 Weeks of Treatment   [ Time Frame: Baseline and 76 weeks ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame From signing of the informed consent until 7 days (inclusive) after last treatment
Additional Description For all safety analyses (except drug-related AEs), patients are assigned to the treatment group “as treated” at inclusion (if a patient erroneously receives the wrong trial drug, the patient is analysed as per the first treatment received). For drug-related AEs, patients are assigned to the actual treatment at onset of AE.

Reporting Groups
  Description
Empagliflozin 10 mg (Drug Naive)

Patients rolled over from trial 1245.20

Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Drug Naive)

Patients rolled over from trial 1245.20

Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Drug Naive)

Patients rolled over from trial 1245.20

Placebo tablets matching Empagliflozin / Sitagliptin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Sitagliptin

Placebo: Placebo matching Empagliflozin 25 mg

Sitagliptin 100mg (Drug Naive)

Patients rolled over from trial 1245.20

Sitagliptin once daily

Placebo: Placebo matching Empagliflozin 25 mg

Placebo: Placebo matching Empagliflozin 10 mg

Sitagliptin 100mg: Sitagliptin once daily

Empagliflozin 10 mg (Pioglitazone)

Patients rolled over from trial 1245.19

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Pioglitazone)

Patients rolled over from trial 1245.19

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Pioglitazone)

Patients rolled over from trial 1245.19

Placebo tablets matching Empagliflozin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg (Metformin)

Patients rolled over from trial 1245.23

Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg: Empagliflozin 10 mg once daily

Empagliflozin 25 mg (Metformin)

Patients rolled over from trial 1245.23

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Metformin)

Patients rolled over from trial 1245.23

Placebo tablets matching Empagliflozin once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 10 mg (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Empagliflozin 10 mg tablets once daily

Empagliflozin 10 mg: Empagliflozin 10 mg tablets once daily

Placebo: Placebo matching Empagliflozin 25 mg

Empagliflozin 25 mg (Metformin+Sulfonylurea)

Patients rolled over from trial 1245.23

Empagliflozin 25 mg tablets once daily

Empagliflozin 25 mg: Empagliflozin 25 mg tablets once daily

Placebo: Placebo matching Empagliflozin 10 mg

Placebo (Metformin+Sulfonylurea)

Patients rolled over from 1245.23

Placebo tablets matching Empagliflozin

Placebo: Placebo matching Empagliflozin 10 mg

Placebo: Placebo matching Empagliflozin 25 mg


Serious Adverse Events
    Empagliflozin 10 mg (Drug Naive)     Empagliflozin 25 mg (Drug Naive)     Placebo (Drug Naive)     Sitagliptin 100mg (Drug Naive)     Empagliflozin 10 mg (Pioglitazone)     Empagliflozin 25 mg (Pioglitazone)     Placebo (Pioglitazone)     Empagliflozin 10 mg (Metformin)     Empagliflozin 25 mg (Metformin)     Placebo (Metformin)     Empagliflozin 10 mg (Metformin+Sulfonylurea)     Empagliflozin 25 mg (Metformin+Sulfonylurea)     Placebo (Metformin+Sulfonylurea)  
Total, serious adverse events                            
# participants affected / at risk     23/229 (10.04%)     25/224 (11.16%)     16/223 (7.17%)     18/223 (8.07%)     11/165 (6.67%)     13/165 (7.88%)     15/168 (8.93%)     24/206 (11.65%)     19/217 (8.76%)     17/214 (7.94%)     31/225 (13.78%)     29/224 (12.95%)     24/217 (11.06%)  
Blood and lymphatic system disorders                            
Normochromic normocytic anaemia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Febrile neutropenia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Pancytopenia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cardiac disorders                            
Coronary artery disease † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     2/206 (0.97%)     2/217 (0.92%)     1/214 (0.47%)     0/225 (0.00%)     1/224 (0.45%)     1/217 (0.46%)  
Acute myocardial infarction † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     2/223 (0.90%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     1/214 (0.47%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Angina pectoris † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     1/214 (0.47%)     2/225 (0.89%)     0/224 (0.00%)     1/217 (0.46%)  
Arteriosclerosis coronary artery † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     2/217 (0.92%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Acute coronary syndrome † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Angina unstable † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Atrial fibrillation † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Atrial flutter † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cardio-respiratory arrest † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Myocardial ischaemia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     1/168 (0.60%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cardiac failure † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Cardiac failure congestive † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Congestive cardiomyopathy † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Myocardial infarction † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     1/214 (0.47%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Prinzmetal angina † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Aortic valve stenosis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Stress cardiomyopathy † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Ventricular tachycardia † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cardiogenic shock † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Left ventricular failure † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Acute left ventricular failure † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Congenital, familial and genetic disorders                            
Gilbert's syndrome † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hydrocele † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Phimosis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Syringomyelia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Ear and labyrinth disorders                            
Vertigo positional † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Sudden hearing loss † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Tinnitus † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Vertigo † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Meniere's disease † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Endocrine disorders                            
Empty sella syndrome † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Goitre † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Hyperparathyroidism † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Eye disorders                            
Diabetic retinopathy † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cataract † 1                          
# participants affected / at risk     1/229 (0.44%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Dacryostenosis acquired † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     1/214 (0.47%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Glaucoma † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Lens dislocation † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Retinal detachment † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Retinal vein occlusion † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Vitreous haemorrhage † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Gastrointestinal disorders                            
Gastritis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     2/224 (0.89%)     0/217 (0.00%)  
Haemorrhoids † 1                          
# participants affected / at risk     2/229 (0.87%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Anal fissure † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Constipation † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Oesophageal rupture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Gastric polyps † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Gastric ulcer † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Gastrooesophageal reflux disease † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Inguinal hernia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     1/217 (0.46%)  
Nausea † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Vomiting † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Abdominal hernia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Abdominal pain † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Colitis ulcerative † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Duodenal ulcer † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Faecaloma † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Gastrointestinal haemorrhage † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Intestinal obstruction † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Large intestine polyp † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
General disorders                            
Chest pain † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     1/217 (0.46%)  
Death † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Chest discomfort † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Non-cardiac chest pain † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hernia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Impaired healing † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Sudden death † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hepatobiliary disorders                            
Cholecystitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cholecystitis acute † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Liver injury † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hepatitis toxic † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cholelithiasis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Cirrhosis alcoholic † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Drug-induced liver injury † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Liver disorder † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Jaundice † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Immune system disorders                            
Hypersensitivity † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Infections and infestations                            
Cellulitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     2/165 (1.21%)     1/168 (0.60%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Gastroenteritis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     2/214 (0.93%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Pneumonia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     2/224 (0.89%)     0/217 (0.00%)  
Urinary tract infection † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     2/225 (0.89%)     0/224 (0.00%)     0/217 (0.00%)  
Amoebic colitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Cervicitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Dengue fever † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Pseudomonas infection † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Pyelonephritis acute † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Septic shock † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Urosepsis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Anal abscess † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Appendicitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Gangrene † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Herpes zoster † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Sepsis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Subcutaneous abscess † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Atypical pneumonia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Cytomegalovirus infection † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Genital infection † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Herpes virus infection † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Infected skin ulcer † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Infective exacerbation of chronic obstructive airways disease † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Listeria sepsis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Peritonitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Pulmonary tuberculosis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Salmonellosis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Schistosomiasis † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Upper respiratory tract infection † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Injury, poisoning and procedural complications                            
Ankle fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Comminuted fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Fall † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     1/206 (0.49%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Hand fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Humerus fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Injury † 1                          
# participants affected / at risk     1/229 (0.44%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Joint dislocation † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Road traffic accident † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Traumatic fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Upper limb fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Facial bones fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Femur fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Hip fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Ligament rupture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     1/214 (0.47%)     0/225 (0.00%)     0/224 (0.00%)     1/217 (0.46%)  
Tendon rupture † 1                          
# participants affected / at risk     1/229 (0.44%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     1/214 (0.47%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Tibia fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     1/223 (0.45%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Animal bite † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Femoral neck fracture † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Ligament sprain † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Meniscus injury † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Multiple fractures † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Muscle strain † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Neck injury † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Post-traumatic neck syndrome † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Subdural haematoma † 1                          
# participants affected / at risk     0/229 (0.00%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Investigations                            
Haemoglobin decreased † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     1/165 (0.61%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Blood creatine phosphokinase increased † 1                          
# participants affected / at risk     1/229 (0.44%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Blood creatinine increased † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Smear cervix abnormal † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Metabolism and nutrition disorders                            
Dehydration † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     1/214 (0.47%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Lactic acidosis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     1/214 (0.47%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Diabetes mellitus inadequate control † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     0/224 (0.00%)     0/217 (0.00%)  
Diabetic ketoacidosis † 1                          
# participants affected / at risk     1/229 (0.44%)     1/224 (0.45%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hyperglycaemia † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hyperlipidaemia † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Hyponatraemia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Insulin-requiring type 2 diabetes mellitus † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Musculoskeletal and connective tissue disorders                            
Osteoarthritis † 1                          
# participants affected / at risk     2/229 (0.87%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     2/206 (0.97%)     1/217 (0.46%)     1/214 (0.47%)     1/225 (0.44%)     0/224 (0.00%)     2/217 (0.92%)  
Spondylolisthesis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     2/225 (0.89%)     0/224 (0.00%)     0/217 (0.00%)  
Arthralgia † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Back pain † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Joint swelling † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Musculoskeletal chest pain † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Osteoarthropathy † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     1/165 (0.61%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Periarthritis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     1/168 (0.60%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Foot deformity † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Intervertebral disc protrusion † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     1/224 (0.45%)     1/217 (0.46%)  
Lumbar spinal stenosis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     1/225 (0.44%)     1/224 (0.45%)     1/217 (0.46%)  
Musculoskeletal pain † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     1/206 (0.49%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Rotator cuff syndrome † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Spinal osteoarthritis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     1/217 (0.46%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Femoroacetabular impingement † 1                          
# participants affected / at risk     1/229 (0.44%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Intervertebral disc disorder † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     0/223 (0.00%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     1/224 (0.45%)     0/217 (0.00%)  
Plica syndrome † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)     0/214 (0.00%)     0/225 (0.00%)     0/224 (0.00%)     0/217 (0.00%)  
Synovitis † 1                          
# participants affected / at risk     0/229 (0.00%)     0/224 (0.00%)     0/223 (0.00%)     1/223 (0.45%)     0/165 (0.00%)     0/165 (0.00%)     0/168 (0.00%)     0/206 (0.00%)     0/217 (0.00%)