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: April 3, 2014
Last verified: April 2014
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  
Number of Participants  
[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  
Number of 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 ]
Results not yet reported.   Anticipated Reporting Date:   01/2014   Safety Issue:   No


  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.


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