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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00968812
First received: August 28, 2009
Last updated: September 19, 2016
Last verified: September 2016
Results First Received: April 17, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Glimepiride
Drug: Canagliflozin (JNJ-28431754)
Drug: Metformin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Canagliflozin 100 mg: Baseline to Week 104 Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Canagliflozin 300 mg: Baseline to Week 104 Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Glimepiride: 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.

Participant Flow:   Overall Study
    Canagliflozin 100 mg: Baseline to Week 104   Canagliflozin 300 mg: Baseline to Week 104   Glimepiride: Baseline to Week 104
STARTED   483   485   482 
COMPLETED   343   323   314 
NOT COMPLETED   140   162   168 
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 
Not specified                25                37                40 



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

Reporting Groups
  Description
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Glimepiride Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.
Total Total of all reporting groups

Baseline Measures
   Canagliflozin 100 mg   Canagliflozin 300 mg   Glimepiride   Total 
Overall Participants Analyzed 
[Units: Participants]
 483   485   482   1450 
Age 
[Units: Participants]
       
<=18 years   0   0   0   0 
Between 18 and 65 years   397   411   399   1207 
>=65 years   86   74   83   243 
Age 
[Units: Years]
Mean (Standard Deviation)
 56.4  (9.49)   55.8  (9.17)   56.3  (9.01)   56.2  (9.22) 
Gender 
[Units: Participants]
       
Female   231   244   219   694 
Male   252   241   263   756 
Region Enroll 
[Units: 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 


  Outcome Measures
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1.  Primary:   Change in HbA1c From Baseline to Week 52   [ Time Frame: Day 1 (Baseline) and Week 52 ]

2.  Secondary:   Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52   [ Time Frame: Day 1 (Baseline) and Week 52 ]
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Measure Type Secondary
Measure Title Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52
Measure 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  
Safety Issue Yes  

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.
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.

Reporting Groups
  Description
Canagliflozin 100 mg Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Canagliflozin 300 mg Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily with protocol-specified doses of metformin for 104 weeks.
Glimepiride Each patient received glimepiride, at protocol-specified doses, once daily in combination with protocol-specified doses of metformin for 104 weeks.

Measured Values
   Canagliflozin 100 mg   Canagliflozin 300 mg   Glimepiride 
Participants Analyzed 
[Units: Participants]
 483   485   482 
Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52 
[Units: Percentage of patients]
 5.6   4.9   34.2 


Statistical Analysis 1 for Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52
Groups [1] Canagliflozin 100 mg vs. Glimepiride
Method [2] Regression, Logistic
P Value [3] <0.001
Odds Ratio (OR) [4] 0.10
95% Confidence Interval 0.06 to 0.16
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Patients Experiencing at Least 1 Hypoglycemic Event From Baseline to Week 52
Groups [1] Canagliflozin 300 mg vs. Glimepiride
Method [2] Regression, Logistic
P Value [3] <0.001
Odds Ratio (OR) [4] 0.09
95% Confidence Interval 0.05 to 0.14
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Percent Change in Body Weight From Baseline to Week 52   [ Time Frame: Day 1 (Baseline) and Week 52 ]

4.  Secondary:   Change in HbA1c From Baseline to Week 104   [ Time Frame: Baseline, Week 104 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No notable study limitations were identified by the Sponsor.


  More Information