Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes Mellitus, Type 2, Canagliflozin, Placebo, Hemoglobin A1c, Type 2 diabetes mellitus
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.
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.
Interventions
DRUGSitagliptin
One 100 mg over-encapsulated tablet orally once daily beginning at Week 26 until Week 52 (Main Study)
DRUGCanagliflozin
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)
DRUGPlacebo
One matching placebo capsule orally once daily for 26 weeks (Main Study)
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
| 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 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. |
Countries
Austria, Colombia, Estonia, Guatemala, Iceland, India, Lithuania, Malaysia, Mexico, Philippines, Poland, Puerto Rico, Romania, South Africa, South Korea, Spain, Sweden, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Main Study: Placebo/Sitagliptin 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. | 192 |
| Main Study: Canagliflozin 100 mg In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks. | 195 |
| Main Study: Canagliflozin 300 mg In the Main Study, each patient received 300 mg of canagliflozin once daily for 52 weeks. | 197 |
| High Glycemic Substudy: Canagliflozin 100 mg In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks. | 47 |
| High Glycemic Substudy: Canagliflozin 300 mg In the High Glycemic Substudy, each patient received 300 mg of canagliflozin once daily for 26 weeks. | 44 |
| Total | 675 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Core Period: Baseline to Week 26 | Adverse Event | 2 | 5 | 3 | 1 | 1 |
| Core Period: Baseline to Week 26 | Death | 1 | 0 | 0 | 0 | 0 |
| Core Period: Baseline to Week 26 | Lack of efficacy on rescue therapy | 3 | 1 | 0 | 0 | 0 |
| Core Period: Baseline to Week 26 | Lost to Follow-up | 2 | 2 | 5 | 0 | 0 |
| Core Period: Baseline to Week 26 | Noncompliance with study drug | 3 | 4 | 2 | 2 | 0 |
| Core Period: Baseline to Week 26 | Other | 4 | 4 | 3 | 1 | 0 |
| Core Period: Baseline to Week 26 | Pregnancy | 1 | 0 | 0 | 0 | 0 |
| Core Period: Baseline to Week 26 | Protocol Violation | 0 | 4 | 0 | 0 | 2 |
| Core Period: Baseline to Week 26 | Unable to take rescue therapy | 1 | 0 | 0 | 0 | 0 |
| Core Period: Baseline to Week 26 | Withdrawal by Subject | 15 | 3 | 9 | 3 | 1 |
| Extension Period: Week 26 to Week 52 | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Creatinine or eGFR withdrawal criteria | 1 | 4 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Death | 1 | 0 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Lack of efficacy on rescue therapy | 7 | 1 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Lost to Follow-up | 4 | 4 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Other | 4 | 5 | 4 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Physician Decision | 0 | 1 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Unable to take rescue therapy | 1 | 0 | 1 | 0 | 0 |
| Extension Period: Week 26 to Week 52 | Withdrawal by Subject | 1 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 42 Participants | 39 Participants | 37 Participants | 5 Participants | 3 Participants | 126 Participants |
| Age, Categorical Between 18 and 65 years | 150 Participants | 156 Participants | 160 Participants | 42 Participants | 41 Participants | 549 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 10.88 | 55.1 years STANDARD_DEVIATION 10.83 | 55.3 years STANDARD_DEVIATION 10.17 | 49.7 years STANDARD_DEVIATION 11.12 | 48.8 years STANDARD_DEVIATION 10.92 | 54.5 years STANDARD_DEVIATION 10.85 |
| Region of Enrollment AUSTRIA | 1 participants | 2 participants | 1 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment COLOMBIA | 8 participants | 8 participants | 6 participants | 3 participants | 0 participants | 25 participants |
| Region of Enrollment ESTONIA | 6 participants | 5 participants | 5 participants | 0 participants | 0 participants | 16 participants |
| Region of Enrollment GUATEMALA | 10 participants | 10 participants | 13 participants | 9 participants | 10 participants | 52 participants |
| Region of Enrollment ICELAND | 4 participants | 4 participants | 8 participants | 2 participants | 2 participants | 20 participants |
| Region of Enrollment INDIA | 8 participants | 11 participants | 8 participants | 5 participants | 2 participants | 34 participants |
| Region of Enrollment LITHUANIA | 17 participants | 10 participants | 12 participants | 2 participants | 1 participants | 42 participants |
| Region of Enrollment MALAYSIA | 6 participants | 2 participants | 7 participants | 1 participants | 0 participants | 16 participants |
| Region of Enrollment MEXICO | 19 participants | 23 participants | 19 participants | 2 participants | 2 participants | 65 participants |
| Region of Enrollment PHILIPPINES | 3 participants | 4 participants | 6 participants | 4 participants | 4 participants | 21 participants |
| Region of Enrollment POLAND | 1 participants | 4 participants | 3 participants | 0 participants | 0 participants | 8 participants |
| Region of Enrollment ROMANIA | 20 participants | 16 participants | 18 participants | 2 participants | 4 participants | 60 participants |
| Region of Enrollment SOUTH AFRICA | 9 participants | 6 participants | 11 participants | 1 participants | 2 participants | 29 participants |
| Region of Enrollment SOUTH KOREA | 10 participants | 8 participants | 7 participants | 1 participants | 1 participants | 27 participants |
| Region of Enrollment SPAIN | 3 participants | 2 participants | 3 participants | 0 participants | 0 participants | 8 participants |
| Region of Enrollment SWEDEN | 11 participants | 18 participants | 18 participants | 0 participants | 1 participants | 48 participants |
| Region of Enrollment UNITED STATES | 56 participants | 62 participants | 52 participants | 15 participants | 15 participants | 200 participants |
| Sex: Female, Male Female | 104 Participants | 114 Participants | 108 Participants | 24 Participants | 25 Participants | 375 Participants |
| Sex: Female, Male Male | 88 Participants | 81 Participants | 89 Participants | 23 Participants | 19 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 192 | 39 / 195 | 51 / 197 | 63 / 192 | 54 / 195 | 69 / 197 | 6 / 47 | 6 / 44 |
| serious Total, serious adverse events | 4 / 192 | 8 / 195 | 2 / 197 | 11 / 192 | 11 / 195 | 5 / 197 | 0 / 47 | 1 / 44 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy) | -2.13 Percent | Standard Error 0.22 |
| Canagliflozin 300 mg | Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy) | -2.56 Percent | Standard Error 0.227 |
Primary
Change in HbA1c From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in HbA1c From Baseline to Week 26 (Main Study) | 0.14 Percent | Standard Error 0.065 |
| Canagliflozin 100 mg | Change in HbA1c From Baseline to Week 26 (Main Study) | -0.77 Percent | Standard Error 0.065 |
| Canagliflozin 300 mg | Change in HbA1c From Baseline to Week 26 (Main Study) | -1.03 Percent | Standard Error 0.064 |
p-value: <0.00195% CI: [-1.088, -0.729]ANCOVA
p-value: <0.00195% CI: [-1.342, -0.985]ANCOVA
Secondary
Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy) | -118 mg/dL | Standard Error 10.179 |
| Canagliflozin 300 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy) | -126 mg/dL | Standard Error 9.437 |
Secondary
Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study) | 5.19 mg/dL | Standard Error 4.204 |
| Canagliflozin 100 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study) | -42.9 mg/dL | Standard Error 3.763 |
| Canagliflozin 300 mg | Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study) | -58.8 mg/dL | Standard Error 3.741 |
p-value: <0.00195% CI: [-59.12, -36.99]ANCOVA
p-value: <0.00195% CI: [-75.02, -52.94]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy) | -81.7 mg/dL | Standard Error 6.459 |
| Canagliflozin 300 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy) | -86.3 mg/dL | Standard Error 6.553 |
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study) | 8.33 mg/dL | Standard Error 2.448 |
| Canagliflozin 100 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study) | -27.2 mg/dL | Standard Error 2.412 |
| Canagliflozin 300 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study) | -35.0 mg/dL | Standard Error 2.391 |
p-value: <0.00195% CI: [-42.22, -28.78]ANCOVA
p-value: <0.00195% CI: [-50.06, -36.69]ANCOVA
Secondary
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy) | -4.47 mmHg | Standard Error 1.754 |
| Canagliflozin 300 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy) | -4.97 mmHg | Standard Error 1.8 |
Secondary
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study) | 0.38 mmHg | Standard Error 0.78 |
| Canagliflozin 100 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study) | -3.34 mmHg | Standard Error 0.775 |
| Canagliflozin 300 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study) | -5.04 mmHg | Standard Error 0.769 |
p-value: <0.00195% CI: [-5.86, -1.568]ANCOVA
p-value: <0.00195% CI: [-7.556, -3.28]ANCOVA
Secondary
Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Canagliflozin 100 mg | Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy) | 17.4 Percentage of patients |
| Canagliflozin 300 mg | Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy) | 11.6 Percentage of patients |
Secondary
Percentage of Patients With HbA1c <7% at Week 26 (Main Study)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With HbA1c <7% at Week 26 (Main Study) | 20.6 Percentage of patients |
| Canagliflozin 100 mg | Percentage of Patients With HbA1c <7% at Week 26 (Main Study) | 44.5 Percentage of patients |
| Canagliflozin 300 mg | Percentage of Patients With HbA1c <7% at Week 26 (Main Study) | 62.4 Percentage of patients |
p-value: <0.00195% CI: [3.1, 9.23]Regression, Logistic
p-value: <0.00195% CI: [8.14, 26.25]Regression, Logistic
Secondary
Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy) | -3.0 Percent change | Standard Error 0.6 |
| Canagliflozin 300 mg | Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy) | -3.8 Percent change | Standard Error 0.6 |
Secondary
Percent Change in Body Weight From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Body Weight From Baseline to Week 26 (Main Study) | -0.6 Percent change | Standard Error 0.2 |
| Canagliflozin 100 mg | Percent Change in Body Weight From Baseline to Week 26 (Main Study) | -2.8 Percent change | Standard Error 0.2 |
| Canagliflozin 300 mg | Percent Change in Body Weight From Baseline to Week 26 (Main Study) | -3.9 Percent change | Standard Error 0.2 |
p-value: <0.00195% CI: [-2.9, -1.6]ANCOVA
p-value: <0.00195% CI: [-4, -2.6]ANCOVA
Secondary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy) | 2.4 Percent change | Standard Error 2.9 |
| Canagliflozin 300 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy) | 10.8 Percent change | Standard Error 2.9 |
Secondary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study) | 4.4 Percent change | Standard Error 1.4 |
| Canagliflozin 100 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study) | 11.2 Percent change | Standard Error 1.4 |
| Canagliflozin 300 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study) | 10.5 Percent change | Standard Error 1.4 |
p-value: <0.00195% CI: [2.9, 10.6]ANCOVA
p-value: 0.00295% CI: [2.2, 9.9]ANCOVA
Secondary
Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canagliflozin 100 mg | Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy) | -0.6 Percent change | Standard Error 7.4 |
| Canagliflozin 300 mg | Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy) | -12.7 Percent change | Standard Error 7.5 |
Secondary
Percent Change in Triglycerides From Baseline to Week 26 (Main Study)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Triglycerides From Baseline to Week 26 (Main Study) | 7.8 Percent change | Standard Error 3.5 |
| Canagliflozin 100 mg | Percent Change in Triglycerides From Baseline to Week 26 (Main Study) | 2.5 Percent change | Standard Error 3.3 |
| Canagliflozin 300 mg | Percent Change in Triglycerides From Baseline to Week 26 (Main Study) | -2.4 Percent change | Standard Error 3.3 |
p-value: 0.26795% CI: [-14.8, 4.1]ANCOVA
p-value: 0.03495% CI: [-19.6, -0.8]ANCOVA