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CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00968812
Recruitment Status : Completed
First Posted : August 31, 2009
Results First Posted : June 4, 2013
Last Update Posted : January 30, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Glimepiride
Drug: Canagliflozin (JNJ-28431754)
Drug: Metformin
Enrollment 1452
Recruitment Details This study evaluated the efficacy and safety of canagliflozin (JNJ-28431754) compared with glimepiride in participants with type 2 diabetes mellitus with inadequate glycemic control despite metformin treatment. The study was conducted between 28 August 2009 and 25 January 2013 and included 157 study centers in 19 countries worldwide.
Pre-assignment Details 1,452 participants were randomly allocated to the 3 treatment arms. 1450 participants received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and safety analysis set. Participant flow is presented for Baseline to Week 104.
Arm/Group Title Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104 Glimepiride: Baseline to Week 104
Hide Arm/Group Description Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Period Title: Overall Study
Started 483 485 482
Completed 343 323 314
Not Completed 140 162 168
Reason Not Completed
Adverse Event             30             46             33
Death             2             2             1
Lack of Efficacy             9             7             16
Lost to Follow-up             17             12             11
Physician Decision             8             5             9
Protocol Violation             7             4             3
Withdrawal by Subject             17             23             25
Creatinine or eGFR withdrawal criteria             9             13             7
Noncompliance with study drug             4             1             6
Unable to take rescue therapy             12             12             17
Other             25             37             40
Arm/Group Title Canagliflozin 100 mg Canagliflozin 300 mg Glimepiride Total
Hide Arm/Group Description Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks. Total of all reporting groups
Overall Number of Baseline Participants 483 485 482 1450
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 483 participants 485 participants 482 participants 1450 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
397
  82.2%
411
  84.7%
399
  82.8%
1207
  83.2%
>=65 years
86
  17.8%
74
  15.3%
83
  17.2%
243
  16.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 483 participants 485 participants 482 participants 1450 participants
56.4  (9.49) 55.8  (9.17) 56.3  (9.01) 56.2  (9.22)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 483 participants 485 participants 482 participants 1450 participants
Female
231
  47.8%
244
  50.3%
219
  45.4%
694
  47.9%
Male
252
  52.2%
241
  49.7%
263
  54.6%
756
  52.1%
Region Enroll  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 483 participants 485 participants 482 participants 1450 participants
ARGENTINA 18 18 18 54
BULGARIA 7 7 7 21
CANADA 19 20 19 58
COSTA RICA 10 9 9 28
DENMARK 24 25 25 74
FINLAND 18 17 19 54
GERMANY 6 7 6 19
INDIA 55 55 56 166
ISRAEL 14 15 14 43
MEXICO 24 25 24 73
NORWAY 9 9 9 27
PHILIPPINES 14 13 13 40
POLAND 14 15 15 44
ROMANIA 43 43 44 130
RUSSIAN FEDERATION 23 22 22 67
SLOVAKIA 15 14 13 42
SOUTH KOREA 31 32 31 94
UKRAINE 22 22 22 66
UNITED STATES 117 117 116 350
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 52
Hide Description The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change.
Time Frame Day 1 (Baseline) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
Arm/Group Title Canagliflozin 100 mg Canagliflozin 300 mg Glimepiride
Hide Arm/Group Description:
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Overall Number of Participants Analyzed 478 474 473
Least Squares Mean (Standard Error)
Unit of Measure: Percent
-0.82  (0.039) -0.93  (0.039) -0.81  (0.039)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Canagliflozin 100 mg, Glimepiride
Comments If the hypothesis of non-inferiority of canagliflozin to glimepiride at Week 52 was demonstrated (ie, upper bound of the 95% Confidence Interval of the treatment difference [canagliflozin minus glimepiride] was less than 0.3) and the upper bound was less than 0.0, the superiority of the canagliflozin dose relative to glimepiride would be concluded.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculation: assuming a difference between canagliflozin and glimepiride of 0.0% and a common standard deviation of 1.0%, and using a 2-sample, 1-sided t-test with a Type I error rate of 0.0125, and assuming a drop-out rate of 35% in 52 weeks, it was estimated that approximately 427 patients per group would provide 90% power to demonstrate non-inferiority with the non-inferiority margin of 0.3, comparing canagliflozin with glimepiride.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.109 to 0.085
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.050
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Canagliflozin 300 mg, Glimepiride
Comments If the hypothesis of non-inferiority of canagliflozin to glimepiride at Week 52 was demonstrated (ie, upper bound of the 95% Confidence Interval of the treatment difference [canagliflozin minus glimepiride] was less than 0.3) and the upper bound was less than 0.0, the superiority of the canagliflozin dose relative to glimepiride would be concluded.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Power calculation: assuming a difference between canagliflozin and glimepiride of 0.0% and a common standard deviation of 1.0%, and using a 2-sample, 1-sided t-test with a Type I error rate of 0.0125, and assuming a drop-out rate of 35% in 52 weeks, it was estimated that approximately 427 patients per group would provide 90% power to demonstrate non-inferiority with the non-inferiority margin of 0.3, comparing canagliflozin with glimepiride
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.217 to -0.023
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.050
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52
Hide Description The table below shows the percentage of patients who experienced at least 1 documented hypoglycemic event from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in percentages.
Time Frame Day 1 (Baseline) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
Arm/Group Title Canagliflozin 100 mg Canagliflozin 300 mg Glimepiride
Hide Arm/Group Description:
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Overall Number of Participants Analyzed 483 485 482
Measure Type: Number
Unit of Measure: Percentage of patients
5.6 4.9 34.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Canagliflozin 100 mg, Glimepiride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
0.06 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Canagliflozin 300 mg, Glimepiride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
0.05 to 0.14
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change in Body Weight From Baseline to Week 52
Hide Description The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean percent change.
Time Frame Day 1 (Baseline) and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 52 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.
Arm/Group Title Canagliflozin 100 mg Canagliflozin 300 mg Glimepiride
Hide Arm/Group Description:
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Overall Number of Participants Analyzed 479 480 478
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-4.2  (0.2) -4.7  (0.2) 1.0  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Canagliflozin 100 mg, Glimepiride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -5.2
Confidence Interval (2-Sided) 95%
-5.7 to -4.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Canagliflozin 300 mg, Glimepiride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -5.7
Confidence Interval (2-Sided) 95%
-6.2 to -5.1
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in HbA1c From Baseline to Week 104
Hide Description The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 104 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus glimepiride) in the LS mean change.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug).
Arm/Group Title Canagliflozin 100 mg Canagliflozin 300 mg Glimepiride
Hide Arm/Group Description:
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Overall Number of Participants Analyzed 478 474 474
Least Squares Mean (Standard Error)
Unit of Measure: Percent
-0.65  (0.042) -0.74  (0.042) -0.55  (0.043)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Canagliflozin 100 mg, Glimepiride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.200 to 0.010
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.054
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Canagliflozin 300 mg, Glimepiride
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.289 to -0.078
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.054
Estimation Comments [Not Specified]
Time Frame Adverse event data were collected for the duration of the study (104 weeks).
Adverse Event Reporting Description

The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.

MEDDRA 14.1 used for Week 52 / MEDDRA 15.0 for Week 104 results.

 
Arm/Group Title Canagliflozin 100 mg: Baseline to Week 52 Canagliflozin 300 mg: Baseline to Week 52 Glimepiride: Baseline to Week 52 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104 Glimepiride: Baseline to Week 104
Hide Arm/Group Description Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Data are presented for Baseline to Week 52. Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Data are presented for Baseline to Week 52. Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks. Data are presented for Baseline to Week 52. Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Data are presented for Baseline to Week 104. Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks. Data are presented for Baseline to Week 104. Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks. Data are presented for Baseline to Week 104.
All-Cause Mortality
Canagliflozin 100 mg: Baseline to Week 52 Canagliflozin 300 mg: Baseline to Week 52 Glimepiride: Baseline to Week 52 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104 Glimepiride: Baseline to Week 104
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Canagliflozin 100 mg: Baseline to Week 52 Canagliflozin 300 mg: Baseline to Week 52 Glimepiride: Baseline to Week 52 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104 Glimepiride: Baseline to Week 104
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   24/483 (4.97%)   26/485 (5.36%)   39/482 (8.09%)   47/483 (9.73%)   47/485 (9.69%)   69/482 (14.32%) 
Blood and lymphatic system disorders             
Anaemia * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Cardiac disorders             
Acute coronary syndrome * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Angina pectoris * 1  1/483 (0.21%)  2/485 (0.41%)  2/482 (0.41%)  3/483 (0.62%)  2/485 (0.41%)  3/482 (0.62%) 
Angina unstable * 1  0/483 (0.00%)  1/485 (0.21%)  1/482 (0.21%)  1/483 (0.21%)  1/485 (0.21%)  2/482 (0.41%) 
Aortic valve incompetence * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Atrial fibrillation * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%) 
Bundle branch block left * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Cardiac arrest * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Cardiomyopathy * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Coronary artery disease * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  1/483 (0.21%)  0/485 (0.00%)  2/482 (0.41%) 
Diabetic cardiomyopathy * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Mitral valve incompetence * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Myocardial infarction * 1  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%)  2/483 (0.41%)  1/485 (0.21%)  1/482 (0.21%) 
Myocardial ischaemia * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Pericardial effusion * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Tachycardia * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Ventricular arrhythmia * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Acute myocardial infarction * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  2/482 (0.41%) 
Cardiac failure * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Coronary artery occlusion * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Congenital, familial and genetic disorders             
Arnold-Chiari malformation * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Philmosis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Eye disorders             
Angle closure glaucoma * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Cataract * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  2/482 (0.41%) 
Diabetic retinopathy * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Vitreous haemorrhage * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Gastrointestinal disorders             
Abdominal pain * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Duodenal ulcer * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Duodenitis * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Inguinal hernia * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%) 
Pancreatitis * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  1/485 (0.21%)  1/482 (0.21%) 
Small intestinal perforation * 1 [1]  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%) 
Umbilical hernia * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Abdominal strangulated herina * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Gastrointestinal haemorrhage * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Pancreatitis acute * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Pancreatitis chronic * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
General disorders             
Asthenia * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Non-cardiac chest pain * 1  0/483 (0.00%)  1/485 (0.21%)  2/482 (0.41%)  0/483 (0.00%)  2/485 (0.41%)  3/482 (0.62%) 
Oedema peripheral * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Cyst * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Hepatobiliary disorders             
Cholecystitis acute * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  1/485 (0.21%)  1/482 (0.21%) 
Cholelithiasis * 1  0/483 (0.00%)  0/485 (0.00%)  3/482 (0.62%)  0/483 (0.00%)  0/485 (0.00%)  4/482 (0.83%) 
Hepatic cyst * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Cholecystitis chronic * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  2/483 (0.41%)  0/485 (0.00%)  0/482 (0.00%) 
Infections and infestations             
Appendicitis * 1  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%)  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%) 
Endometritis * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Gastroenteritis * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Localised infection * 1 [2]  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Lobar pneumonia * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Lower respiratory tract infection * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Lung infection * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Pneumonia * 1  1/483 (0.21%)  1/485 (0.21%)  2/482 (0.41%)  1/483 (0.21%)  2/485 (0.41%)  2/482 (0.41%) 
Postoperative wound infection * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Respiratory tract infection viral * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Staphylococcal infection * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Urinary tract infection * 1  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%)  1/483 (0.21%)  2/485 (0.41%)  1/482 (0.21%) 
Herpes zoster * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Orchitis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Pyelonephritis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Upper respiratory tract infection * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Sepsis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Infection * 1 [2]  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%) 
Injury, poisoning and procedural complications             
Eye injury * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Fall * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Femoral neck fracture * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Foot fracture * 1  1/483 (0.21%)  0/485 (0.00%)  1/482 (0.21%)  1/483 (0.21%)  0/485 (0.00%)  1/482 (0.21%) 
Incisional hernia * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Injury * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Ligament sprain * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  2/483 (0.41%)  0/485 (0.00%)  0/482 (0.00%) 
Lower limb fracture * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Meniscus lesion * 1  2/483 (0.41%)  0/485 (0.00%)  0/482 (0.00%)  2/483 (0.41%)  0/485 (0.00%)  0/482 (0.00%) 
Muscle injury * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Muscle rupture * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Overdose * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Road traffic accident * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%) 
Skull fracture * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Subdural haematoma * 1  1/483 (0.21%)  0/485 (0.00%)  1/482 (0.21%)  1/483 (0.21%)  0/485 (0.00%)  1/482 (0.21%) 
Toxicity to various agents * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Ulna fracture * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Wrist fracture * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Chemical poisoning * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Clavicle fracture * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%) 
Concussion * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Contusion * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Femur fracture * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Head injury * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Heat exhaustion * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Humerus fracture * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Joint dislocation * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Procedural complication * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Procedural nausea * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Investigations             
Blood creatinine increased * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Electrocardiogram T wave biphasic * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Metabolism and nutrition disorders             
Dehydration * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Diabetes mellitus inadequate control * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Hyperglycaemia * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Obesity * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Musculoskeletal and connective tissue disorders             
Intervertebral disc protrusion * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Musculoskeletal pain * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Pain in extremity * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Spinal column stenosis * 1  1/483 (0.21%)  0/485 (0.00%)  1/482 (0.21%)  2/483 (0.41%)  0/485 (0.00%)  1/482 (0.21%) 
Arthritis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Osteoarthritis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Polyarthritis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Endometrial cancer * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Renal cancer stage I * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Squamous cell carcinoma of the cervix * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Uterine leiomyoma * 1  0/483 (0.00%)  2/485 (0.41%)  0/482 (0.00%)  0/483 (0.00%)  3/485 (0.62%)  0/482 (0.00%) 
Breast cancer stage I * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Colon cancer * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Gastrointestinal tract adenoma * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Hepatic neoplasm * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Lung neoplasm * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Oesophageal carcinoma * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Prostate cancer * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  1/482 (0.21%) 
Nervous system disorders             
Carotid arterial embolus * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Cerebral infarction * 1  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%)  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%) 
Cerebrovascular accident * 1  2/483 (0.41%)  1/485 (0.21%)  0/482 (0.00%)  2/483 (0.41%)  1/485 (0.21%)  2/482 (0.41%) 
Hemiplegic migraine * 1 [3]  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%) 
Vertebrobasilar insufficiency * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Complex regional pain syndrome * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Dizziness * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Haemorrhage intracranial * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Hemiparesis * 1 [3]  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Syncope * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Transient ischaemic attack * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  1/485 (0.21%)  1/482 (0.21%) 
Psychiatric disorders             
Confusional state * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Stress * 1 [4]  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%) 
Anxiety * 1 [4]  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Renal and urinary disorders             
Incontinence * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Calculus ureteric * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Nephrolithiasis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Renal failure acute * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Urethral stenosis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Urinary retention * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Reproductive system and breast disorders             
Dysfunctional uterine bleeding * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Menstrual disorder * 1  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Benign prostatic hyperplasia * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  1/482 (0.21%) 
Prostatitis * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Prostatomegaly * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Respiratory, thoracic and mediastinal disorders             
Allergic bronchitis * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Chronic obstructive pulmonary disease * 1  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%)  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%) 
Dyspnoea * 1  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%)  0/483 (0.00%)  0/485 (0.00%)  2/482 (0.41%) 
Interstitial lung disease * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Pulmonary oedema * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Pulmonary embolism * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Skin and subcutaneous tissue disorders             
Urticaria * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Diabetic foot * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  1/485 (0.21%)  0/482 (0.00%) 
Social circumstances             
Familial risk factor * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/482 (0.00%) 
Surgical and medical procedures             
Small bowel perforation * 1 [5]  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
Vascular disorders             
Deep vein thrombosis * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Haematoma * 1  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Hypertension * 1  0/483 (0.00%)  1/485 (0.21%)  1/482 (0.21%)  1/483 (0.21%)  1/485 (0.21%)  1/482 (0.21%) 
Hypertensive crisis * 2  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%)  0/483 (0.00%)  0/485 (0.00%)  1/482 (0.21%) 
Intermittent claudication * 1  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%)  1/483 (0.21%)  0/485 (0.00%)  0/482 (0.00%) 
Hypotension * 1  0/483 (0.00%)  0/485 (0.00%)  0/482 (0.00%)  0/483 (0.00%)  1/485 (0.21%)  0/482 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MEDDRA 14.1 / 15.0
2
Term from vocabulary, MEDDRA 14.1
[1]
This event was re-coded as "Small bowel perforation"; it was subsequently re-mapped to the "Surgical and medical procedures".
[2]
In the Week 52 study report, this event was coded as "infection"; it was subsequently re-coded in the Week 104 study report as "localised infection".
[3]
In the Week 52 study report, this event was coded as "Hemiplegic migraine"; it was subsequently re-coded in the Week 104 study report as "Hemiparesis".
[4]
In the Week 52 study report, this event was coded as "stress"; it was subsequently re-coded in the Week 104 study report as "anxiety".
[5]
In Week 52 study report this event was coded as "small intestinal perforation" and was mapped under "Gastrointestinal disorders ".
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Canagliflozin 100 mg: Baseline to Week 52 Canagliflozin 300 mg: Baseline to Week 52 Glimepiride: Baseline to Week 52 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104 Glimepiride: Baseline to Week 104
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   138/483 (28.57%)   150/485 (30.93%)   175/482 (36.31%)   198/483 (40.99%)   204/485 (42.06%)   242/482 (50.21%) 
Gastrointestinal disorders             
Diarrhoea * 1  24/483 (4.97%)  33/485 (6.80%)  29/482 (6.02%)  25/482 (5.19%)  39/485 (8.04%)  34/482 (7.05%) 
Nausea * 1  16/483 (3.31%)  25/485 (5.15%)  13/482 (2.70%)  20/483 (4.14%)  27/485 (5.57%)  19/482 (3.94%) 
Infections and infestations             
Nasopharyngitis * 1  33/483 (6.83%)  37/485 (7.63%)  37/482 (7.68%)  47/483 (9.73%)  55/485 (11.34%)  51/482 (10.58%) 
Upper respiratory tract infection * 1  17/483 (3.52%)  27/485 (5.57%)  41/482 (8.51%)  36/483 (7.45%)  38/485 (7.84%)  56/482 (11.62%) 
Urinary tract infection * 1  26/483 (5.38%)  23/485 (4.74%)  18/482 (3.73%)  44/483 (9.11%)  33/485 (6.80%)  27/482 (5.60%) 
Influenza * 1  14/483 (2.90%)  17/485 (3.51%)  7/482 (1.45%)  25/483 (5.18%)  23/485 (4.74%)  13/482 (2.70%) 
Metabolism and nutrition disorders             
Hypoglycaemia * 1  15/483 (3.11%)  9/485 (1.86%)  61/482 (12.66%)  17/483 (3.52%)  16/485 (3.30%)  86/482 (17.84%) 
Musculoskeletal and connective tissue disorders             
Back pain * 1  29/483 (6.00%)  18/485 (3.71%)  20/482 (4.15%)  34/483 (7.04%)  28/485 (5.77%)  26/482 (5.39%) 
Arthralgia * 1  18/483 (3.73%)  13/485 (2.68%)  18/482 (3.73%)  26/483 (5.38%)  16/485 (3.30%)  24/482 (4.98%) 
Nervous system disorders             
Headache * 1  14/483 (2.90%)  25/485 (5.15%)  24/482 (4.98%)  21/483 (4.35%)  29/485 (5.98%)  33/482 (6.85%) 
Vascular disorders             
Hypertension * 1  8/483 (1.66%)  10/485 (2.06%)  13/482 (2.70%)  15/483 (3.11%)  11/485 (2.27%)  30/482 (6.22%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MEDDRA 14.1 / 15.0
No notable study limitations were identified by the Sponsor.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise
Organization: Janssen Research & Development, LLC
Phone: 1-800-526-7736
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00968812    
Other Study ID Numbers: CR016480
28431754DIA3009 ( Other Identifier: Janssen Research & Development, LLC )
2009-009320-36 ( EudraCT Number )
First Submitted: August 28, 2009
First Posted: August 31, 2009
Results First Submitted: April 17, 2013
Results First Posted: June 4, 2013
Last Update Posted: January 30, 2017