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An Efficacy, Safety, and Tolerability Study of Canagliflozin (JNJ-28431754) in Patients With Type 2 Diabetes

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: NCT00642278
Recruitment Status : Completed
First Posted : March 25, 2008
Results First Posted : May 17, 2013
Last Update Posted : July 19, 2013
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Diabetes Mellitus, Type II
Diabetes Mellitus, Non Insulin Dependent
Interventions Drug: Canagliflozin (JNJ-28431754)
Drug: Sitagliptin
Drug: Placebo
Enrollment 451
Recruitment Details This study evaluated the efficacy and safety of canagliflozin (JNJ-28431754) in patients with type 2 diabetes mellitus with sitagliptin as a reference arm. The study was conducted between 27 March 2008 and 28 January 2009 and recruited patients from 85 study centers located in 13 countries worldwide.
Pre-assignment Details A total of 451 patients were randomly allocated to the 7 treatment arms in the study and comprised the intent-to-treat analysis set which was used for the efficacy analyses. All 451 patients received at least 1 dose of study drug and were included in the safety analysis set.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description Each patient received matching placebo twice daily for 12 weeks. Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks. Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Period Title: Overall Study
Started 65 64 64 65 64 64 65
Completed 55 59 59 56 56 57 60
Not Completed 10 5 5 9 8 7 5
Reason Not Completed
Adverse Event             2             1             3             1             2             2             0
Lack of Efficacy             0             1             0             0             0             0             0
Lost to Follow-up             5             1             0             1             0             1             1
Physician Decision             0             0             0             1             0             0             0
Protocol Violation             0             0             1             1             0             1             2
Withdrawal by Subject             1             1             1             3             6             2             2
Noncompliance with study drug regimen             0             0             0             1             0             0             0
Other             2             1             0             1             0             1             0
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily Total
Hide Arm/Group Description Each patient received matching placebo twice daily for 12 weeks. Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks. Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Total of all reporting groups
Overall Number of Baseline Participants 65 64 64 65 64 64 65 451
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 64 participants 65 participants 64 participants 64 participants 65 participants 451 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
63
  96.9%
61
  95.3%
63
  98.4%
61
  93.8%
63
  98.4%
62
  96.9%
65
 100.0%
438
  97.1%
>=65 years
2
   3.1%
3
   4.7%
1
   1.6%
4
   6.2%
1
   1.6%
2
   3.1%
0
   0.0%
13
   2.9%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 64 participants 64 participants 65 participants 64 participants 64 participants 65 participants 451 participants
53.3  (7.82) 53.3  (8.48) 51.7  (7.95) 52.9  (9.56) 52.3  (6.88) 55.2  (7.14) 51.7  (8.09) 52.9  (8.06)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 64 participants 65 participants 64 participants 64 participants 65 participants 451 participants
Female
34
  52.3%
30
  46.9%
28
  43.8%
32
  49.2%
28
  43.8%
36
  56.3%
27
  41.5%
215
  47.7%
Male
31
  47.7%
34
  53.1%
36
  56.3%
33
  50.8%
36
  56.3%
28
  43.8%
38
  58.5%
236
  52.3%
Region Enroll  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 64 participants 65 participants 64 participants 64 participants 65 participants 451 participants
ARGENTINA 1 1 3 1 2 0 2 10
BULGARIA 1 1 1 0 3 3 1 10
CANADA 11 6 9 8 8 4 7 53
CZECH REPUBLIC 2 3 2 6 0 2 2 17
INDIA 4 6 3 5 2 6 4 30
MALAYSIA 3 0 6 2 4 1 3 19
MEXICO 4 6 9 9 6 14 2 50
POLAND 3 5 4 7 6 5 9 39
ROMANIA 9 8 4 6 6 5 8 46
RUSSIAN FEDERATION 5 7 5 2 6 3 4 32
UNITED KINGDOM 1 0 2 1 3 1 2 10
UNITED STATES 21 21 16 18 18 20 21 135
1.Primary Outcome
Title Change in HbA1c From Baseline to Week 12
Hide Description The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame Day 1 (Baseline) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description:
Each patient received matching placebo twice daily for 12 weeks.
Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Overall Number of Participants Analyzed 61 62 62 62 60 62 62
Mean (Standard Deviation)
Unit of Measure: Percent
-0.22  (0.702) -0.79  (0.749) -0.76  (0.992) -0.70  (0.720) -0.92  (0.695) -0.95  (0.704) -0.74  (0.615)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 50 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted using Dunnett's procedure.
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-0.747 to -0.148
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.116
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted using Dunnett's procedure.
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.804 to -0.207
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.116
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 200 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted using Dunnett's procedure.
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.841 to -0.244
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.116
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted using Dunnett's procedure.
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.71
Confidence Interval (2-Sided) 95%
-1.006 to -0.405
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.117
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted using Dunnett's procedure.
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.73
Confidence Interval (2-Sided) 95%
-1.029 to -0.432
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.116
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Adjusted using Dunnett's procedure.
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.862 to -0.265
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.116
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12
Hide Description The table below shows the mean change in FPG from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame Day 1 (Baseline) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description:
Each patient received matching placebo twice daily for 12 weeks.
Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Overall Number of Participants Analyzed 62 63 63 62 61 62 64
Mean (Standard Deviation)
Unit of Measure: mmol/L
0.2  (1.58) -0.9  (2.26) -1.4  (1.70) -1.5  (2.23) -1.4  (1.87) -1.3  (1.54) -0.7  (1.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 50 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.39 to -0.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-1.98 to -0.92
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 200 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-2.33 to -1.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-2.32 to -1.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Twice Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-2.25 to -1.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-1.51 to -0.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.27
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Patients With Symptoms of Hypoglycemia
Hide Description The table below shows the percentage of patients who experienced symptomatic hypoglycemic events between Baseline and Week 12.
Time Frame Up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomiy assigned to a treatment group.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description:
Each patient received matching placebo twice daily for 12 weeks.
Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Overall Number of Participants Analyzed 65 64 64 65 64 64 65
Measure Type: Number
Unit of Measure: Percentage of patients
2 0 2 6 0 3 5
4.Secondary Outcome
Title Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12
Hide Description The table below shows the mean change in overnight urine glucose/creatinine ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame Day 1 (Baseline) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description:
Each patient received matching placebo twice daily for 12 weeks.
Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Overall Number of Participants Analyzed 54 58 56 53 57 56 58
Mean (Standard Deviation)
Unit of Measure: mg/mg
1.9  (12.34) 35.4  (28.98) 51.5  (28.83) 50.5  (24.38) 49.4  (38.41) 61.6  (37.85) -1.9  (14.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 50 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value 36.1
Confidence Interval (2-Sided) 95%
26.07 to 46.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value 49.3
Confidence Interval (2-Sided) 95%
39.17 to 59.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 200 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value 48.2
Confidence Interval (2-Sided) 95%
37.98 to 58.42
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value 49.0
Confidence Interval (2-Sided) 95%
38.91 to 59.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Twice Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value 60.3
Confidence Interval (2-Sided) 95%
50.17 to 70.35
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.513
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-13.33 to 6.67
Parameter Dispersion
Type: Standard Error of the mean
Value: 5.09
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Absolute Change in Body Weight From Baseline to Week 12
Hide Description The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group.
Time Frame Day 1 (Baseline) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description:
Each patient received matching placebo twice daily for 12 weeks.
Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Overall Number of Participants Analyzed 62 63 64 63 62 62 64
Mean (Standard Deviation)
Unit of Measure: kg
-0.78  (2.099) -1.96  (2.334) -2.25  (2.145) -2.32  (2.842) -2.88  (2.391) -2.87  (2.344) -0.43  (2.693)
6.Secondary Outcome
Title Percent Change in Body Weight From Baseline to Week 12
Hide Description The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
Time Frame Day 1 (Baseline) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description:
Each patient received matching placebo twice daily for 12 weeks.
Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
Overall Number of Participants Analyzed 62 63 64 63 62 62 64
Mean (Standard Deviation)
Unit of Measure: Percent change
-1.1  (2.4) -2.3  (2.8) -2.6  (2.3) -2.7  (3.0) -3.4  (2.8) -3.4  (2.6) -0.6  (3.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 50 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.2 to -0.3
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-2.5 to -0.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 200 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and mixed meal tolerance test.
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-2.6 to -0.7
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-3.3 to -1.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg Twice Daily
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 ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-3.3 to -1.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Sitagliptin 100 mg Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.371
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model included terms for treatment, baseline value, and stratification factor (participation in mixed meal tolerance test).
Method of Estimation Estimation Parameter Least-Sqaures Mean Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.5 to 1.4
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.5
Estimation Comments [Not Specified]
Time Frame Adverse events were reported for the duration of the study; each patient participated in the study for approximately 12 weeks.
Adverse Event Reporting Description The total number of adverse events listed in the "Other (non-Serious) Adverse Event" 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.
 
Arm/Group Title Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Hide Arm/Group Description Each patient received matching placebo twice daily for 12 weeks. Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening). Each patient received 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks. Each patient received 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
All-Cause Mortality
Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/65 (1.54%)   1/64 (1.56%)   1/64 (1.56%)   1/65 (1.54%)   1/64 (1.56%)   1/64 (1.56%)   0/65 (0.00%) 
Cardiac disorders               
Atrial fibrillation * 1  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  1/64 (1.56%)  0/64 (0.00%)  0/65 (0.00%) 
Cardiac failure congestive * 1  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  1/64 (1.56%)  0/64 (0.00%)  0/65 (0.00%) 
Infections and infestations               
Gastroenteritis * 1  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  0/64 (0.00%)  1/64 (1.56%)  0/65 (0.00%) 
Otitis externa * 1  0/65 (0.00%)  1/64 (1.56%)  0/64 (0.00%)  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%) 
Pneumonia * 1  1/65 (1.54%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%) 
Investigations               
Blood creatine phosphokinase increased * 1  1/65 (1.54%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%) 
Metabolism and nutrition disorders               
Gestational diabetes * 1  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  1/65 (1.54%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%) 
Musculoskeletal and connective tissue disorders               
Spondylolisthesis * 1  0/65 (0.00%)  0/64 (0.00%)  1/64 (1.56%)  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Hypoxia * 1  1/65 (1.54%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MEDDRA 11.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Canagliflozin 50 mg Daily Canagliflozin 100 mg Daily Canagliflozin 200 mg Daily Canagliflozin 300 mg Daily Canagliflozin 300 mg Twice Daily Sitagliptin 100 mg Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/65 (13.85%)   13/64 (20.31%)   10/64 (15.63%)   10/65 (15.38%)   10/64 (15.63%)   12/64 (18.75%)   7/65 (10.77%) 
Gastrointestinal disorders               
Abdominal pain upper * 1  1/65 (1.54%)  0/64 (0.00%)  0/64 (0.00%)  0/65 (0.00%)  2/64 (3.13%)  4/64 (6.25%)  0/65 (0.00%) 
Nausea * 1  0/65 (0.00%)  3/64 (4.69%)  1/64 (1.56%)  1/65 (1.54%)  3/64 (4.69%)  5/64 (7.81%)  1/65 (1.54%) 
Infections and infestations               
Nasopharyngitis * 1  2/65 (3.08%)  5/64 (7.81%)  0/64 (0.00%)  0/65 (0.00%)  1/64 (1.56%)  1/64 (1.56%)  3/65 (4.62%) 
Urinary tract infection * 1  4/65 (6.15%)  3/64 (4.69%)  2/64 (3.13%)  6/65 (9.23%)  2/64 (3.13%)  3/64 (4.69%)  1/65 (1.54%) 
Vulvovaginal mycotic infection * 1  0/65 (0.00%)  4/64 (6.25%)  2/64 (3.13%)  4/65 (6.15%)  1/64 (1.56%)  3/64 (4.69%)  1/65 (1.54%) 
Nervous system disorders               
Headache * 1  2/65 (3.08%)  1/64 (1.56%)  5/64 (7.81%)  2/65 (3.08%)  3/64 (4.69%)  1/64 (1.56%)  1/65 (1.54%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MEDDRA 11.1
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
Layout table for additonal information
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00642278    
Other Study ID Numbers: CR014587
28431754DIA2001 ( Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. )
First Submitted: March 21, 2008
First Posted: March 25, 2008
Results First Submitted: April 1, 2013
Results First Posted: May 17, 2013
Last Update Posted: July 19, 2013