The CANTATA-M (CANagliflozin Treatment and Trial Analysis - Monotherapy) Trial
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01081834
Collaborator
(none)
678
79
3
24
8.6
0.4
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of 2 different doses of canagliflozin administered as monotherapy compared with placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double blind (neither the patient or the study doctor will know the name of the assigned treatment), parallel-group, 3 arm (patients will be assigned to 1 of 3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients diagnosed with T2DM who are not achieving an adequate response from diet and exercise to control their diabetes. Approximately 450 patients with inadequate glycemic control with diet and exercise will receive once-daily treatment with canagliflozin 100 mg or 300 mg once daily for 52 weeks or 26 weeks of double-blind treatment with placebo followed by 26 weeks of sitagliptin 100 mg (sitagliptin is an antihyperglycemic agent that will allow patients randomized to the placebo group to improve glycemic control and remain in the study). Patients will participate in the study for approximately 60 to 68 weeks (referred to as the Main Study). The study will also include a High Glycemic Substudy in 50 to 100 patients with T2DM who have poorer glycemic control with diet and exercise. Patients in the substudy will be assigned to receive double-blind canagliflozin 100 mg or 300 mg for 26 weeks and the total duration of patient participatation in the substudy will be approximately 34 to 42 weeks. During treatment, if a patient's fasting blood sugar remains high despite treatment with study drug and reinforcement with diet and exercise, the patient will receive treatment with metformin (rescue therapy) consistent with local prescribing information. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. Patients will take single blind placebo for 1 or 2 weeks (wks) before randomization to the Main Study or the High Glycemic Substudy.
Study Design
Study Type:
Interventional
Actual Enrollment
:
678 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin as Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise
Study Start Date
:
Mar 1, 2010
Actual Primary Completion Date
:
Aug 1, 2011
Actual Study Completion Date
:
Mar 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Canagliflozin 100 mg Each patient will receive 100 mg of canagliflozin once daily for 52 weeks (Main Study) or 26 weeks only (High Glycemic Substudy). |
Drug: Canagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks (Main Study) or 26 weeks (High Glycemic Substudy)
|
| Experimental: Canagliflozin 300 mg Each patient will receive 300 mg of canagliflozin once daily for 52 weeks (Main Study) or 26 weeks only (High Glycemic Substudy). |
Drug: Canagliflozin
One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks (Main Study) or 26 weeks (High Glycemic Substudy)
|
| Experimental: Placebo/Sitagliptin In the Main Study, each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52. |
Drug: Placebo
One matching placebo capsule orally once daily for 26 weeks (Main Study)
Drug: Sitagliptin
One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 (Main Study)
|
Outcome Measures
Primary Outcome Measures
- Change in HbA1c From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
- Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
Secondary Outcome Measures
- Percentage of Patients With HbA1c <7% at Week 26 (Main Study) [Week 26]
The table below shows the percentage of patients with HbA1c <7% at Week 26. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
- Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
- Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
- Percent Change in Body Weight From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
- Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.
- Percent Change in Triglycerides From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
- Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
- Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy) [Week 26]
The table below shows the percentage of patients with HbA1c <7% at Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
- Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
- Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
- Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
- Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
- Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares mean percent change in triglycerides from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
- Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy) [Day 1 (Baseline) and Week 26]
The table below shows the least-squares mean percent change in HDL-C from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
All patients must have a diagnosis of T2DM
-
Patients in the main study must have a Hemoglobin A1c (HbA1c) between >=7% and <=10% and a fasting plasma glucose (FPG) <270 mg/dL (15 mmol/L)
-
Patients in the High Glycemic Cohort Substudy must have an HbA1c between >10% and <=12% and a FPG <=350 mg/dL (19.44 mmol/L)
Exclusion Criteria:
- History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix | Arizona | United States | ||
| 2 | Concord | California | United States | ||
| 3 | Greenbrae | California | United States | ||
| 4 | Los Angeles | California | United States | ||
| 5 | Spring Valley | California | United States | ||
| 6 | Colorado Springs | Colorado | United States | ||
| 7 | Denver | Colorado | United States | ||
| 8 | Northglenn | Colorado | United States | ||
| 9 | Springfield | Illinois | United States | ||
| 10 | Evansville | Indiana | United States | ||
| 11 | Baton Rouge | Louisiana | United States | ||
| 12 | Metairie | Louisiana | United States | ||
| 13 | Meridian | New Jersey | United States | ||
| 14 | Albuquerque | New Mexico | United States | ||
| 15 | New York | New York | United States | ||
| 16 | West Seneca | New York | United States | ||
| 17 | Mooresville | North Carolina | United States | ||
| 18 | Perryopolis | Pennsylvania | United States | ||
| 19 | Pittsburgh | Pennsylvania | United States | ||
| 20 | Taylors | South Carolina | United States | ||
| 21 | Dallas | Texas | United States | ||
| 22 | Houston | Texas | United States | ||
| 23 | San Antonio | Texas | United States | ||
| 24 | Norfolk | Virginia | United States | ||
| 25 | Horn | Austria | |||
| 26 | Salzburg | Austria | |||
| 27 | Wien | Austria | |||
| 28 | Barranquilla | Colombia | |||
| 29 | Bogota | Colombia | |||
| 30 | Pärnu | Estonia | |||
| 31 | Tartu | Estonia | |||
| 32 | Viljandi | Estonia | |||
| 33 | Guatemala | Guatemala | |||
| 34 | Reykjavik | Iceland | |||
| 35 | Bangalore | India | |||
| 36 | Hyderabad | India | |||
| 37 | Nagpur | India | |||
| 38 | Busan | Korea, Republic of | |||
| 39 | Goyang-Si | Korea, Republic of | |||
| 40 | Jeonju-Si | Korea, Republic of | |||
| 41 | Seoul | Korea, Republic of | |||
| 42 | Wonju-Si | Korea, Republic of | |||
| 43 | Kaunas | Lithuania | |||
| 44 | Klaipeda | Lithuania | |||
| 45 | Siauliai | Lithuania | |||
| 46 | Vilnius Lt | Lithuania | |||
| 47 | Vilnius | Lithuania | |||
| 48 | Kelantan | Malaysia | |||
| 49 | Kuala Lumpur N/A | Malaysia | |||
| 50 | Kuala Lumpur | Malaysia | |||
| 51 | Aguascalientes | Mexico | |||
| 52 | Guadalajara | Mexico | |||
| 53 | Mex | Mexico | |||
| 54 | Monterrey | Mexico | |||
| 55 | Zapopan | Mexico | |||
| 56 | Makati | Philippines | |||
| 57 | Manila | Philippines | |||
| 58 | Marikina City | Philippines | |||
| 59 | Pasay | Philippines | |||
| 60 | Katowice | Poland | |||
| 61 | Torun | Poland | |||
| 62 | Warszawa | Poland | |||
| 63 | Fajardo | Puerto Rico | |||
| 64 | Ponce | Puerto Rico | |||
| 65 | San Juan | Puerto Rico | |||
| 66 | Baia Mare | Romania | |||
| 67 | Brasov | Romania | |||
| 68 | Bucharest | Romania | |||
| 69 | Targu Mures | Romania | |||
| 70 | Halfway | South Africa | |||
| 71 | Pretoria | South Africa | |||
| 72 | Alcala De Henares | Spain | |||
| 73 | Elche | Spain | |||
| 74 | Girona | Spain | |||
| 75 | Pozuelo De Alarcon | Spain | |||
| 76 | Göteborg | Sweden | |||
| 77 | Lund | Sweden | |||
| 78 | Malmö | Sweden | |||
| 79 | Skene | Sweden |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01081834
Other Study ID Numbers:
- CR017011
- 28431754DIA3005
First Posted:
Mar 5, 2010
Last Update Posted:
Feb 23, 2017
Last Verified:
Jun 1, 2013
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study evaluated the efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. The study was conducted between 08 February 2010 and 18 August 2011 and recruited patients from 90 study centers in 17 countries worldwide. |
|---|---|
| Pre-assignment Detail | 678 patients were enrolled into the study; 587 patients in the main study and 91 patients in the high glycemic substudy. 584 patients in the main study and all 91 patients in the high glycemic substudy received at least one dose of study drug and were included in the modified intent-to-treat (mITT) analyses sets and the safety analyses sets. |
| Arm/Group Title | Main Study: Placebo/Sitagliptin | Main Study: Canagliflozin 100 mg | Main Study: Canagliflozin 300 mg | High Glycemic Substudy: Canagliflozin 100 mg | High Glycemic Substudy: Canagliflozin 300 mg |
|---|---|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each patient received 300 mg of canagliflozin once daily for 52 weeks. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks only. No patients received treatment during the period Week 26 to Week 52. | In the High Glycemic Substudy, each patient received 300 mg of canagliflozin once daily for 26 weeks only. No patients received treatment during the period Week 26 to Week 52. |
| Period Title: Core Period: Baseline to Week 26 | |||||
| STARTED | 192 | 195 | 197 | 47 | 44 |
| COMPLETED | 160 | 172 | 175 | 40 | 40 |
| NOT COMPLETED | 32 | 23 | 22 | 7 | 4 |
| Period Title: Core Period: Baseline to Week 26 | |||||
| STARTED | 155 | 170 | 170 | 0 | 0 |
| COMPLETED | 135 | 152 | 165 | 0 | 0 |
| NOT COMPLETED | 20 | 18 | 5 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Main Study: Placebo/Sitagliptin | Main Study: Canagliflozin 100 mg | Main Study: Canagliflozin 300 mg | High Glycemic Substudy: Canagliflozin 100 mg | High Glycemic Substudy: Canagliflozin 300 mg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each patient received 300 mg of canagliflozin once daily for 52 weeks. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each patient received 300 mg of canagliflozin once daily for 26 weeks. | Total of all reporting groups |
| Overall Participants | 192 | 195 | 197 | 47 | 44 | 675 |
| Age (Count of Participants) | ||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
150
78.1%
|
156
80%
|
160
81.2%
|
42
89.4%
|
41
93.2%
|
549
81.3%
|
| >=65 years |
42
21.9%
|
39
20%
|
37
18.8%
|
5
10.6%
|
3
6.8%
|
126
18.7%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
55.7
(10.88)
|
55.1
(10.83)
|
55.3
(10.17)
|
49.7
(11.12)
|
48.8
(10.92)
|
54.5
(10.85)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
104
54.2%
|
114
58.5%
|
108
54.8%
|
24
51.1%
|
25
56.8%
|
375
55.6%
|
| Male |
88
45.8%
|
81
41.5%
|
89
45.2%
|
23
48.9%
|
19
43.2%
|
300
44.4%
|
| Region of Enrollment (participants) [Number] | ||||||
| AUSTRIA |
1
0.5%
|
2
1%
|
1
0.5%
|
0
0%
|
0
0%
|
4
0.6%
|
| COLOMBIA |
8
4.2%
|
8
4.1%
|
6
3%
|
3
6.4%
|
0
0%
|
25
3.7%
|
| ESTONIA |
6
3.1%
|
5
2.6%
|
5
2.5%
|
0
0%
|
0
0%
|
16
2.4%
|
| GUATEMALA |
10
5.2%
|
10
5.1%
|
13
6.6%
|
9
19.1%
|
10
22.7%
|
52
7.7%
|
| ICELAND |
4
2.1%
|
4
2.1%
|
8
4.1%
|
2
4.3%
|
2
4.5%
|
20
3%
|
| INDIA |
8
4.2%
|
11
5.6%
|
8
4.1%
|
5
10.6%
|
2
4.5%
|
34
5%
|
| LITHUANIA |
17
8.9%
|
10
5.1%
|
12
6.1%
|
2
4.3%
|
1
2.3%
|
42
6.2%
|
| MALAYSIA |
6
3.1%
|
2
1%
|
7
3.6%
|
1
2.1%
|
0
0%
|
16
2.4%
|
| MEXICO |
19
9.9%
|
23
11.8%
|
19
9.6%
|
2
4.3%
|
2
4.5%
|
65
9.6%
|
| PHILIPPINES |
3
1.6%
|
4
2.1%
|
6
3%
|
4
8.5%
|
4
9.1%
|
21
3.1%
|
| POLAND |
1
0.5%
|
4
2.1%
|
3
1.5%
|
0
0%
|
0
0%
|
8
1.2%
|
| ROMANIA |
20
10.4%
|
16
8.2%
|
18
9.1%
|
2
4.3%
|
4
9.1%
|
60
8.9%
|
| SOUTH AFRICA |
9
4.7%
|
6
3.1%
|
11
5.6%
|
1
2.1%
|
2
4.5%
|
29
4.3%
|
| SOUTH KOREA |
10
5.2%
|
8
4.1%
|
7
3.6%
|
1
2.1%
|
1
2.3%
|
27
4%
|
| SPAIN |
3
1.6%
|
2
1%
|
3
1.5%
|
0
0%
|
0
0%
|
8
1.2%
|
| SWEDEN |
11
5.7%
|
18
9.2%
|
18
9.1%
|
0
0%
|
1
2.3%
|
48
7.1%
|
| UNITED STATES |
56
29.2%
|
62
31.8%
|
52
26.4%
|
15
31.9%
|
15
34.1%
|
200
29.6%
|
Outcome Measures
| Title | Change in HbA1c From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 189 | 191 | 194 |
| Least Squares Mean (Standard Error) [Percent] |
0.14
(0.065)
|
-0.77
(0.065)
|
-1.03
(0.064)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.91 | |
| Confidence Interval |
(2-Sided) 95% -1.088 to -0.729 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.091 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.16 | |
| Confidence Interval |
(2-Sided) 95% -1.342 to -0.985 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.091 |
|
| Estimation Comments | ||
| Title | Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 46 | 43 |
| Least Squares Mean (Standard Error) [Percent] |
-2.13
(0.220)
|
-2.56
(0.227)
|
| Title | Percentage of Patients With HbA1c <7% at Week 26 (Main Study) |
|---|---|
| Description | The table below shows the percentage of patients with HbA1c <7% at Week 26. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. |
| Time Frame | Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 189 | 191 | 194 |
| Number [Percentage of patients] |
20.6
|
44.5
|
62.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 5.34 | |
| Confidence Interval |
(2-Sided) 95% 3.10 to 9.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 14.61 | |
| Confidence Interval |
(2-Sided) 95% 8.14 to 26.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 184 | 188 | 192 |
| Least Squares Mean (Standard Error) [mg/dL] |
8.33
(2.448)
|
-27.2
(2.412)
|
-35.0
(2.391)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -35.5 | |
| Confidence Interval |
(2-Sided) 95% -42.22 to -28.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.420 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -43.4 | |
| Confidence Interval |
(2-Sided) 95% -50.06 to -36.69 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.402 |
|
| Estimation Comments | ||
| Title | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 126 | 154 | 157 |
| Least Squares Mean (Standard Error) [mg/dL] |
5.19
(4.204)
|
-42.9
(3.763)
|
-58.8
(3.741)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -49.1 | |
| Confidence Interval |
(2-Sided) 95% -59.12 to -36.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.629 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -64.0 | |
| Confidence Interval |
(2-Sided) 95% -75.02 to -52.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.616 |
|
| Estimation Comments | ||
| Title | Percent Change in Body Weight From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 190 | 192 | 194 |
| Least Squares Mean (Standard Error) [Percent change] |
-0.6
(0.2)
|
-2.8
(0.2)
|
-3.9
(0.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -2.2 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to -1.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -3.3 | |
| Confidence Interval |
(2-Sided) 95% -4.0 to -2.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
| Title | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 190 | 192 | 195 |
| Least Squares Mean (Standard Error) [mmHg] |
0.38
(0.780)
|
-3.34
(0.775)
|
-5.04
(0.769)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -3.71 | |
| Confidence Interval |
(2-Sided) 95% -5.860 to -1.568 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.093 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -5.42 | |
| Confidence Interval |
(2-Sided) 95% -7.556 to -3.280 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.088 |
|
| Estimation Comments | ||
| Title | Percent Change in Triglycerides From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 171 | 183 | 183 |
| Least Squares Mean (Standard Error) [Percent change] |
7.8
(3.5)
|
2.5
(3.3)
|
-2.4
(3.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.267 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -5.3 | |
| Confidence Interval |
(2-Sided) 95% -14.8 to 4.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.8 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.034 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -10.2 | |
| Confidence Interval |
(2-Sided) 95% -19.6 to -0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.8 |
|
| Estimation Comments | ||
| Title | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study) |
|---|---|
| Description | The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. | In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks. |
| Measure Participants | 170 | 182 | 183 |
| Least Squares Mean (Standard Error) [Percent change] |
4.4
(1.4)
|
11.2
(1.4)
|
10.5
(1.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | 6.7 | |
| Confidence Interval |
(2-Sided) 95% 2.9 to 10.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.9 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | 6.0 | |
| Confidence Interval |
(2-Sided) 95% 2.2 to 9.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.9 |
|
| Estimation Comments | ||
| Title | Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the percentage of patients with HbA1c <7% at Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 46 | 43 |
| Number [Percentage of patients] |
17.4
|
11.6
|
| Title | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 45 | 43 |
| Least Squares Mean (Standard Error) [mg/dL] |
-81.7
(6.459)
|
-86.3
(6.553)
|
| Title | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 30 | 34 |
| Least Squares Mean (Standard Error) [mg/dL] |
-118
(10.179)
|
-126
(9.437)
|
| Title | Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 46 | 43 |
| Least Squares Mean (Standard Error) [Percent change] |
-3.0
(0.6)
|
-3.8
(0.6)
|
| Title | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 46 | 43 |
| Least Squares Mean (Standard Error) [mmHg] |
-4.47
(1.754)
|
-4.97
(1.800)
|
| Title | Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares mean percent change in triglycerides from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic Substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 44 | 43 |
| Least Squares Mean (Standard Error) [Percent change] |
-0.6
(7.4)
|
-12.7
(7.5)
|
| Title | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy) |
|---|---|
| Description | The table below shows the least-squares mean percent change in HDL-C from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy. |
| Time Frame | Day 1 (Baseline) and Week 26 |
Outcome Measure Data
| 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 26 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 | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|
| Arm/Group Description | In the High Glycemic Substudy, no patients received placebo. | In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | In the High Glycemic substudy, each pateint received 300 mg of canagliflozin once daily for 26 weeks. |
| Measure Participants | 0 | 44 | 43 |
| Least Squares Mean (Standard Error) [Percent change] |
2.4
(2.9)
|
10.8
(2.9)
|
Adverse Events
| Time Frame | Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 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. | |||||||||||||||
| Arm/Group Title | Main Study (Baseline to Week 26): Placebo | Main Study (Baseline to Week 26): Cana 100 mg | Main Study (Baseline to Week 26): Cana 300 mg | Main Study (Baseline to Week 52): Placebo/Sitagliptin | Main Study (Baseline to Week 52): Cana 100 mg | Main Study (Baseline to Week 52): Cana 300 mg | High Glycemic Substudy (Baseline to Week 26): Cana 100 mg | High Glycemic Substudy (Baseline to Week 26): Cana 300 mg | ||||||||
| Arm/Group Description | Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Data are presented for Baseline to Week 26. | Each patient received 100 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 26. | Each patient received 300 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 26. | Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Data are presented for Baseline to Week 52. | Each patient received 100 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 52. | Each patient received 300 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 52. | Each patient received 100 mg of canagliflozin (Cana) once daily for 26 weeks. Data are only available for Baseline to Week 26. | Each patient received 300 mg of canagliflozin (Cana) once daily for 26 weeks. Data are only available for Baseline to Week 26. | ||||||||
All Cause Mortality |
||||||||||||||||
| Main Study (Baseline to Week 26): Placebo | Main Study (Baseline to Week 26): Cana 100 mg | Main Study (Baseline to Week 26): Cana 300 mg | Main Study (Baseline to Week 52): Placebo/Sitagliptin | Main Study (Baseline to Week 52): Cana 100 mg | Main Study (Baseline to Week 52): Cana 300 mg | High Glycemic Substudy (Baseline to Week 26): Cana 100 mg | High Glycemic Substudy (Baseline to Week 26): Cana 300 mg | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Main Study (Baseline to Week 26): Placebo | Main Study (Baseline to Week 26): Cana 100 mg | Main Study (Baseline to Week 26): Cana 300 mg | Main Study (Baseline to Week 52): Placebo/Sitagliptin | Main Study (Baseline to Week 52): Cana 100 mg | Main Study (Baseline to Week 52): Cana 300 mg | High Glycemic Substudy (Baseline to Week 26): Cana 100 mg | High Glycemic Substudy (Baseline to Week 26): Cana 300 mg | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/192 (2.1%) | 8/195 (4.1%) | 2/197 (1%) | 11/192 (5.7%) | 11/195 (5.6%) | 5/197 (2.5%) | 0/47 (0%) | 1/44 (2.3%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Coronary artery disease | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Myocardial infarction | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Pericardial effusion | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Intestinal obstruction | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Nausea | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Vomiting | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Abdominal hernia | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Inguinal hernia | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Umbilical hernia | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Hepatobiliary disorders | ||||||||||||||||
| Ischaemic hepatitis | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Liver disorder | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Abscess limb | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Bacterial prostatitis | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Cellulitis | 1/192 (0.5%) | 1/195 (0.5%) | 0/197 (0%) | 1/192 (0.5%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Diverticulitis | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Pneumonia | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Septic shock | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Appendicitis | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Gastrointestinal infection | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Pulmonary tuberculosis | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Viral pericarditis | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||
| Ankle fracture | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Brain herniation | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Wound | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Skeletal injury | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Spinal column injury | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Investigations | ||||||||||||||||
| Hepatic enzyme increased | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 1/44 (2.3%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Osteoarthritis | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Prostate cancer | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Haemorrhage intracranial | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Peripheral sensory neuropathy | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/192 (0.5%) | 0/195 (0%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Renal colic | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Renal failure acute | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Pulmonary embolism | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Asthma | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Urticaria | 0/192 (0%) | 2/195 (1%) | 0/197 (0%) | 0/192 (0%) | 2/195 (1%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Deep vein thrombosis | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/192 (0%) | 0/195 (0%) | 1/197 (0.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Thrombosis | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/192 (0%) | 1/195 (0.5%) | 0/197 (0%) | 0/47 (0%) | 0/44 (0%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Main Study (Baseline to Week 26): Placebo | Main Study (Baseline to Week 26): Cana 100 mg | Main Study (Baseline to Week 26): Cana 300 mg | Main Study (Baseline to Week 52): Placebo/Sitagliptin | Main Study (Baseline to Week 52): Cana 100 mg | Main Study (Baseline to Week 52): Cana 300 mg | High Glycemic Substudy (Baseline to Week 26): Cana 100 mg | High Glycemic Substudy (Baseline to Week 26): Cana 300 mg | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/192 (19.8%) | 39/195 (20%) | 51/197 (25.9%) | 63/192 (32.8%) | 54/195 (27.7%) | 69/197 (35%) | 6/47 (12.8%) | 6/44 (13.6%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Nasopharyngitis | 10/192 (5.2%) | 10/195 (5.1%) | 16/197 (8.1%) | 15/192 (7.8%) | 14/195 (7.2%) | 20/197 (10.2%) | 2/47 (4.3%) | 3/44 (6.8%) | ||||||||
| Upper respiratory tract infection | 11/192 (5.7%) | 7/195 (3.6%) | 9/197 (4.6%) | 18/192 (9.4%) | 8/195 (4.1%) | 14/197 (7.1%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Urinary tract infection | 8/192 (4.2%) | 14/195 (7.2%) | 9/197 (4.6%) | 11/192 (5.7%) | 16/195 (8.2%) | 12/197 (6.1%) | 3/47 (6.4%) | 2/44 (4.5%) | ||||||||
| Influenza | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 7/192 (3.6%) | 12/195 (6.2%) | 8/197 (4.1%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 6/192 (3.1%) | 5/195 (2.6%) | 12/197 (6.1%) | 9/192 (4.7%) | 5/195 (2.6%) | 15/197 (7.6%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Pain in extremity | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 1/47 (2.1%) | 3/44 (6.8%) | ||||||||
| Arthralgia | 0/192 (0%) | 0/195 (0%) | 0/197 (0%) | 13/192 (6.8%) | 10/195 (5.1%) | 3/197 (1.5%) | 0/47 (0%) | 0/44 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Headache | 7/192 (3.6%) | 14/195 (7.2%) | 12/197 (6.1%) | 12/192 (6.3%) | 19/195 (9.7%) | 17/197 (8.6%) | 0/47 (0%) | 0/44 (0%) | ||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | 1-800-526-7736 |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01081834
Other Study ID Numbers:
- CR017011
- 28431754DIA3005
First Posted:
Mar 5, 2010
Last Update Posted:
Feb 23, 2017
Last Verified:
Jun 1, 2013