Diabetes Mellitus, Type 2
Conditions
Keywords
Canagliflozin, Placebo, Hemoglobin A1c, Bone, Type 2 diabetes mellitus
Brief summary
The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in older patients (55 to 80 years of age) with type 2 diabetes mellitus (T2DM) with inadequate control on their current diabetes treatment regimen.
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), placebo-controlled, parallel-group, 3-arm (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 with T2DM who are not achieving an adequate response from current antihyperglycemic therapy to control their diabetes. Approximately 720 older (55 to 80 years of age) patients with T2DM who are either not on an antihyperglycemic agent or who are receiving treatment with a stable regimen of antihyperglycemic agent(s) and have inadequate glycemic (blood sugar) control will receive once daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 104 weeks (includes 26 weeks of double-blind treatment followed by a 78-week extension period). In addition, all patients will take stable doses of the antihyperglycemic agent(s) that they were taking before entry in the study for the duration of the study. Patients will participate in the study for approximately 108 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with an antihyperglycemic agent (rescue therapy) that is considered clinically appropriate and consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, measures of bone health, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. All patients will take single-blind placebo capsules for 2 weeks before randomization. After randomization, patients will take double blind canagliflozin (100 mg or 300 mg) or matching placebo for 104 weeks.
Interventions
One 100 mg over-encapsulated tablet orally (by mouth) once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
One 300 mg over-encapsulated tablet orally (by mouth) once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
DRUGAntihyperglycemic agent(s)
Stable doses of antihyperglycemic agents (sulfonylurea agent, thiazolidinediones, dipeptidyl peptidase 4 \[DPP-4\] inhibitors, metformin, insulin \[all types\]) and their combinations (sulfonylurea agent and insulin \[all types\], metformin and insulin \[all types\], metformin and sulfonylurea, alpha glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 \[DPP-4\]) are used as per protocol specifications.
DRUGPlacebo
One matching placebo capsule orally once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.
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
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* All patients must have a diagnosis of T2DM and may be currently treated with a stable regimen of antihyperglycemic agent(s) * Patients in the study must have a HbA1c between \>=7 and \<=10.0% * Patients must have a fasting plasma glucose (FPG) \<270 mg/dL (15 mmol/L)
Exclusion criteria
* History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | 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. |
| Percent Change in Body Weight From Baseline to Week 26 | 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 change. |
| Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean change in total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | Day 1 (Baseline) and Week 26 | Region percent total fat = body fat as a percentage of (body fat + lean body mass + bone mass content). The table below shows the least-squares (LS) mean change in region percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific dual-energy X-ray absorptiometry (DXA) analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | Day 1 (Baseline) and Week 26 | Tissue percent total fat = body fat as a percentage of body fat + lean body mass. The table below shows the least-squares (LS) mean change in tissue percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | 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. |
| Percentage of Patients With HbA1c <7% at Week 26 | Week 26 | The table below shows the percentage of patients with HbA1c \<7% at Week 26 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage. |
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 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 or each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change. |
| Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in lumbar spine BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. |
| Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in distal forearm BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. |
| Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in femoral neck BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. |
| Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26 | Day 1 (Baseline) and Week 26 | The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in total hip BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in LS mean percent change. |
| Percent Change in Triglycerides From Baseline to Week 26 | 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 change. |
Countries
Australia, Canada, Colombia, France, Greece, Hong Kong, India, New Zealand, Poland, Romania, South Africa, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This study evaluated the efficacy and safety of canagliflozin in older patients with type 2 diabetes mellitus with inadequate control on their current diabetes treatment regimen. The study began on 07 June 2010 and ended on 23 May 2013. Patients were recruited from 90 study centers located in 17 countries worldwide.
Pre-assignment details
716 patients were randomly allocated to the 3 treatment arms. 714 patients received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and safety analysis set. Participant flow is presented for Baseline to Week 104 (Overall Study).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Each patient received matching placebo once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry. | 237 |
| Canagliflozin 100 mg Each patient received 100 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry. | 241 |
| Canagliflozin 300 mg Each patient received 300 mg of canagliflozin once daily for 104 weeks in addition to being on a stable antihyperglycemic (AHA) regimen at the time of study entry. | 236 |
| Total | 714 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 17 | 9 | 23 |
| Overall Study | Death | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 8 | 2 | 6 |
| Overall Study | Noncompliance with study drug | 1 | 0 | 2 |
| Overall Study | Other | 34 | 31 | 21 |
| Overall Study | Physician Decision | 4 | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 7 | 4 |
Baseline characteristics
| Characteristic | Total | Placebo | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 273 Participants | 86 Participants | 100 Participants | 87 Participants |
| Age, Categorical Between 18 and 65 years | 441 Participants | 151 Participants | 141 Participants | 149 Participants |
| Age, Continuous | 63.6 years STANDARD_DEVIATION 6.24 | 63.2 years STANDARD_DEVIATION 6.21 | 64.3 years STANDARD_DEVIATION 6.46 | 63.4 years STANDARD_DEVIATION 5.99 |
| Region of Enrollment AUSTRALIA | 23 participants | 6 participants | 6 participants | 11 participants |
| Region of Enrollment CANADA | 84 participants | 24 participants | 32 participants | 28 participants |
| Region of Enrollment COLOMBIA | 53 participants | 18 participants | 15 participants | 20 participants |
| Region of Enrollment FRANCE | 7 participants | 2 participants | 2 participants | 3 participants |
| Region of Enrollment GREECE | 3 participants | 1 participants | 1 participants | 1 participants |
| Region of Enrollment HONG KONG | 4 participants | 1 participants | 1 participants | 2 participants |
| Region of Enrollment INDIA | 22 participants | 8 participants | 3 participants | 11 participants |
| Region of Enrollment NEW ZEALAND | 37 participants | 16 participants | 10 participants | 11 participants |
| Region of Enrollment POLAND | 37 participants | 11 participants | 12 participants | 14 participants |
| Region of Enrollment ROMANIA | 25 participants | 8 participants | 10 participants | 7 participants |
| Region of Enrollment SOUTH AFRICA | 31 participants | 9 participants | 12 participants | 10 participants |
| Region of Enrollment SPAIN | 13 participants | 2 participants | 3 participants | 8 participants |
| Region of Enrollment SWEDEN | 10 participants | 4 participants | 4 participants | 2 participants |
| Region of Enrollment SWITZERLAND | 4 participants | 2 participants | 2 participants | 0 participants |
| Region of Enrollment UKRAINE | 14 participants | 3 participants | 8 participants | 3 participants |
| Region of Enrollment UNITED KINGDOM | 49 participants | 19 participants | 22 participants | 8 participants |
| Region of Enrollment UNITED STATES | 298 participants | 103 participants | 98 participants | 97 participants |
| Sex: Female, Male Female | 318 Participants | 94 Participants | 117 Participants | 107 Participants |
| Sex: Female, Male Male | 396 Participants | 143 Participants | 124 Participants | 129 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 99 / 237 | 92 / 241 | 98 / 236 | 166 / 237 | 169 / 241 | 169 / 236 |
| serious Total, serious adverse events | 12 / 237 | 10 / 241 | 8 / 236 | 41 / 237 | 40 / 241 | 43 / 236 |
Outcome results
Primary
Change in HbA1c From Baseline to 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.
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 | -0.03 Percent | Standard Error 0.063 |
| Canagliflozin 100 mg | Change in HbA1c From Baseline to Week 26 | -0.60 Percent | Standard Error 0.063 |
| Canagliflozin 300 mg | Change in HbA1c From Baseline to Week 26 | -0.73 Percent | Standard Error 0.064 |
p-value: <0.00195% CI: [-0.841, -0.566]ANCOVA
p-value: <0.00195% CI: [-0.708, -0.436]ANCOVA
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to 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.
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 | 7.39 mg/dL | Standard Error 2.875 |
| Canagliflozin 100 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -18.1 mg/dL | Standard Error 2.86 |
| Canagliflozin 300 mg | Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 | -20.3 mg/dL | Standard Error 2.92 |
p-value: <0.00195% CI: [-31.68, -19.32]ANCOVA
p-value: <0.00195% CI: [-33.97, -21.49]ANCOVA
Secondary
Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Region percent total fat = body fat as a percentage of (body fat + lean body mass + bone mass content). The table below shows the least-squares (LS) mean change in region percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific dual-energy X-ray absorptiometry (DXA) analysis for body composition. 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 Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | 0.00 Percent | Standard Error 0.27 |
| Canagliflozin 100 mg | Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -1.03 Percent | Standard Error 0.268 |
| Canagliflozin 300 mg | Change in Region Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -1.18 Percent | Standard Error 0.261 |
Comparison: Region percent total fatp-value: <0.00195% CI: [-1.633, -0.428]ANCOVA
Comparison: Region percent total fatp-value: <0.00195% CI: [-1.772, -0.587]ANCOVA
Secondary
Change in Systolic Blood Pressure (SBP) From Baseline to 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.
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 | 1.10 mmHg | Standard Error 1.039 |
| Canagliflozin 100 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | -3.52 mmHg | Standard Error 1.035 |
| Canagliflozin 300 mg | Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | -6.79 mmHg | Standard Error 1.056 |
p-value: <0.00195% CI: [-6.854, -2.401]ANCOVA
p-value: <0.00195% CI: [-10.14, -5.641]ANCOVA
Secondary
Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
Tissue percent total fat = body fat as a percentage of body fat + lean body mass. The table below shows the least-squares (LS) mean change in tissue percent total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. 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 Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | 0.02 Percent | Standard Error 0.28 |
| Canagliflozin 100 mg | Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -1.04 Percent | Standard Error 0.278 |
| Canagliflozin 300 mg | Change in Tissue Percent Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -1.18 Percent | Standard Error 0.27 |
p-value: 0.00195% CI: [-1.677, -0.43]ANCOVA
p-value: <0.00195% CI: [-1.812, -0.584]ANCOVA
Secondary
Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition
The table below shows the least-squares (LS) mean change in total fat from Baseline to Week 26 for each treatment group in patients randomized to the subset of patients undergoing specific DXA analysis for body composition. 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 Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -0.28 kg | Standard Error 0.336 |
| Canagliflozin 100 mg | Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -1.87 kg | Standard Error 0.332 |
| Canagliflozin 300 mg | Change in Total Fat From Baseline to Week 26 in a Subset of Patients Undergoing Specific Dual-energy X-ray Absorptiometry (DXA) Analysis for Body Composition | -2.38 kg | Standard Error 0.323 |
p-value: <0.00195% CI: [-2.339, -0.842]ANCOVA
p-value: <0.00195% CI: [-2.833, -1.368]ANCOVA
Secondary
Percentage of Patients With HbA1c <7% at Week 26
The table below shows the percentage of patients with HbA1c \<7% at Week 26 in each treatment group. 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 | 28.0 Percentage of patients |
| Canagliflozin 100 mg | Percentage of Patients With HbA1c <7% at Week 26 | 47.7 Percentage of patients |
| Canagliflozin 300 mg | Percentage of Patients With HbA1c <7% at Week 26 | 58.5 Percentage of patients |
p-value: <0.00195% CI: [1.93, 4.56]Regression, Logistic
p-value: <0.00195% CI: [2.89, 6.95]Regression, Logistic
Secondary
Percent Change in Body Weight From Baseline to 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 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 | -0.1 Percent change | Standard Error 0.3 |
| Canagliflozin 100 mg | Percent Change in Body Weight From Baseline to Week 26 | -2.4 Percent change | Standard Error 0.3 |
| Canagliflozin 300 mg | Percent Change in Body Weight From Baseline to Week 26 | -3.1 Percent change | Standard Error 0.3 |
p-value: <0.00195% CI: [-2.8, -1.7]ANCOVA
p-value: <0.00195% CI: [-3.5, -2.4]ANCOVA
Secondary
Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in distal forearm BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in 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 Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26 | -0.5 Percent change | Standard Error 0.3 |
| Canagliflozin 100 mg | Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26 | -0.7 Percent change | Standard Error 0.3 |
| Canagliflozin 300 mg | Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26 | -0.8 Percent change | Standard Error 0.3 |
95% CI: [-0.9, 0.4]ANCOVA
95% CI: [-1, 0.3]ANCOVA
Secondary
Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in femoral neck BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in 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 Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26 | -1.0 Percent change | Standard Error 0.3 |
| Canagliflozin 100 mg | Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26 | -0.7 Percent change | Standard Error 0.3 |
| Canagliflozin 300 mg | Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26 | -0.6 Percent change | Standard Error 0.3 |
95% CI: [-0.3, 1]ANCOVA
95% CI: [-0.3, 1.1]ANCOVA
Secondary
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 or 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 | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 1.5 Percent change | Standard Error 1.2 |
| Canagliflozin 100 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 6.8 Percent change | Standard Error 1.2 |
| Canagliflozin 300 mg | Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | 6.2 Percent change | Standard Error 1.2 |
p-value: <0.00195% CI: [2.6, 7.9]ANCOVA
p-value: <0.00195% CI: [2, 7.4]ANCOVA
Secondary
Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in lumbar spine BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in 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 Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26 | 0.5 Percent change | Standard Error 0.3 |
| Canagliflozin 100 mg | Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26 | 0.7 Percent change | Standard Error 0.3 |
| Canagliflozin 300 mg | Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26 | 0.2 Percent change | Standard Error 0.3 |
95% CI: [-0.4, 0.8]ANCOVA
95% CI: [-0.9, 0.3]ANCOVA
Secondary
Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
The table below shows the least-squares (LS) mean percent change from Baseline to Week 26 in total hip BMD for each treatment group as assessed by dual-energy X-ray absorptiometry (DXA). The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in 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 Total Hip Bone Mineral Density (BMD) From Baseline to Week 26 | -0.5 Percent change | Standard Error 0.2 |
| Canagliflozin 100 mg | Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26 | -0.9 Percent change | Standard Error 0.2 |
| Canagliflozin 300 mg | Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26 | -1.0 Percent change | Standard Error 0.2 |
95% CI: [-0.8, 0]ANCOVA
95% CI: [-0.9, -0.1]ANCOVA
Secondary
Percent Change in Triglycerides From Baseline to 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 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 | 7.7 Percent change | Standard Error 3.4 |
| Canagliflozin 100 mg | Percent Change in Triglycerides From Baseline to Week 26 | 2.8 Percent change | Standard Error 3.3 |
| Canagliflozin 300 mg | Percent Change in Triglycerides From Baseline to Week 26 | 8.4 Percent change | Standard Error 3.4 |
p-value: 0.19495% CI: [-12.1, 2.5]ANCOVA
p-value: 0.84695% CI: [-6.6, 8.1]ANCOVA