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A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01106651
Collaborator
(none)
716
Enrollment
86
Locations
3
Arms
35
Duration (Months)
8.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Canagliflozin 100 mg
  • Drug: Canagliflozin 300 mg
  • Drug: Antihyperglycemic agent(s)
  • Drug: Placebo
 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), 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
716 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 Compared With Placebo in the Treatment of Older Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Glucose Lowering Therapy
Study Start Date :
Jun 1, 2010
Actual Primary Completion Date :
Nov 1, 2011
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Canagliflozin 100 mg

Each patient will receive 100 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Drug: Canagliflozin 100 mg
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.

Drug: Antihyperglycemic 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.
Experimental: Canagliflozin 300 mg

Each patient will receive 300 mg of canagliflozin once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Drug: Canagliflozin 300 mg
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.

Drug: Antihyperglycemic 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.
Placebo Comparator: Placebo

Each patient will receive matching placebo once daily for 104 weeks with/without stable doses of antihyperglycemic agent(s) taken at the time of study entry.

Drug: Antihyperglycemic 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.

Drug: Placebo
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.

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
55 Years to 80 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Glendale Arizona United States
2 Phoenix Arizona United States
3 Little Rock Arkansas United States
4 Carmichael California United States
5 Citrus Heights California United States
6 Fair Oaks California United States
7 Roseville California United States
8 Sacramento California United States
9 San Diego California United States
10 Walnut Creek California United States
11 Daytona Beach Florida United States
12 Fleming Island Florida United States
13 Jacksonville Florida United States
14 Miami Florida United States
15 Atlanta Georgia United States
16 Wichita Kansas United States
17 Waltham Massachusetts United States
18 Pahrump Nevada United States
19 Albuquerque New Mexico United States
20 Cary North Carolina United States
21 Charlotte North Carolina United States
22 Wilmington North Carolina United States
23 Bismarck North Dakota United States
24 Franklin Ohio United States
25 Mount Pleasant South Carolina United States
26 Bristol Tennessee United States
27 Carrollton Texas United States
28 Dallas Texas United States
29 Irving Texas United States
30 Plano Texas United States
31 Richardson Texas United States
32 Renton Washington United States
33 Tacoma Washington United States
34 Wenatchee Washington United States
35 Fremantle Australia
36 Heidelberg Heights Australia
37 Meadowbrook Australia
38 Richmond Australia
39 Vancouver British Columbia Canada
40 St. John'S Newfoundland and Labrador Canada
41 Barrie Ontario Canada
42 London Ontario Canada
43 Markham Ontario Canada
44 Oakville Ontario Canada
45 Toronto Ontario Canada
46 Montreal Quebec Canada
47 Barranquilla Colombia
48 Bogota Colombia
49 Corbeil Essonnes France
50 Paris France
51 Venissieux France
52 Thessalonikis Greece
53 Thessaloniki Greece
54 Sha Tin Hong Kong
55 Bangalore India
56 Nagpur India
57 Pune India
58 Auckland New Zealand
59 Christchurch New Zealand
60 Tauranga New Zealand
61 Wellington New Zealand
62 Katowice Poland
63 Krakow Poland
64 Torun Poland
65 Warszawa Poland
66 Wroclaw Poland
67 Bucharest Romania
68 Sibiu Romania
69 Pretoria South Africa
70 Granada Spain
71 Madrid Spain
72 Pozuelo De Alarcon Spain
73 Sevilla Spain
74 Göteborg Sweden
75 Uppsala Sweden
76 Bruderholz Switzerland
77 St Gallen Switzerland
78 Kharkov Ukraine
79 Kiev Ukraine
80 Birmingham United Kingdom
81 Cardiff United Kingdom
82 Glasgow United Kingdom
83 Liverpool United Kingdom
84 Manchester United Kingdom
85 Reading United Kingdom
86 Salford United Kingdom

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:
NCT01106651
Other Study ID Numbers:
  • CR017014
  • 28431754DIA3010
First Posted:
Apr 20, 2010
Last Update Posted:
Nov 4, 2014
Last Verified:
Oct 1, 2014
Keywords provided by Janssen Research & Development, LLC
Canagliflozin
Placebo
Hemoglobin A1c
Bone
Type 2 diabetes mellitus
Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Canagliflozin
Hypoglycemic Agents

Study Results

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 Detail 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).
Arm/Group Title Placebo Canagliflozin 100 mg Canagliflozin 300 mg
Arm/Group Description 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. 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. 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.
Period Title: Overall Study
STARTED 237 241 236
COMPLETED 158 184 178
NOT COMPLETED 79 57 58

Baseline Characteristics

Arm/Group Title Placebo Canagliflozin 100 mg Canagliflozin 300 mg Total
Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Participants 237 241 236 714
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
151
63.7%
141
58.5%
149
63.1%
441
61.8%
>=65 years
86
36.3%
100
41.5%
87
36.9%
273
38.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
63.2
(6.21)
64.3
(6.46)
63.4
(5.99)
63.6
(6.24)
Sex: Female, Male (Count of Participants)
Female
94
39.7%
117
48.5%
107
45.3%
318
44.5%
Male
143
60.3%
124
51.5%
129
54.7%
396
55.5%
Region of Enrollment (participants) [Number]
AUSTRALIA
6
2.5%
6
2.5%
11
4.7%
23
3.2%
CANADA
24
10.1%
32
13.3%
28
11.9%
84
11.8%
COLOMBIA
18
7.6%
15
6.2%
20
8.5%
53
7.4%
FRANCE
2
0.8%
2
0.8%
3
1.3%
7
1%
GREECE
1
0.4%
1
0.4%
1
0.4%
3
0.4%
HONG KONG
1
0.4%
1
0.4%
2
0.8%
4
0.6%
INDIA
8
3.4%
3
1.2%
11
4.7%
22
3.1%
NEW ZEALAND
16
6.8%
10
4.1%
11
4.7%
37
5.2%
POLAND
11
4.6%
12
5%
14
5.9%
37
5.2%
ROMANIA
8
3.4%
10
4.1%
7
3%
25
3.5%
SOUTH AFRICA
9
3.8%
12
5%
10
4.2%
31
4.3%
SPAIN
2
0.8%
3
1.2%
8
3.4%
13
1.8%
SWEDEN
4
1.7%
4
1.7%
2
0.8%
10
1.4%
SWITZERLAND
2
0.8%
2
0.8%
0
0%
4
0.6%
UKRAINE
3
1.3%
8
3.3%
3
1.3%
14
2%
UNITED KINGDOM
19
8%
22
9.1%
8
3.4%
49
6.9%
UNITED STATES
103
43.5%
98
40.7%
97
41.1%
298
41.7%

Outcome Measures

1. Primary Outcome
Title Change in HbA1c From Baseline to Week 26
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 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. 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. 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.
Measure Participants 232 239 229
Least Squares Mean (Standard Error) [Percent]
-0.03
(0.063)
-0.60
(0.063)
-0.73
(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 -0.57
Confidence Interval (2-Sided) 95%
-0.708 to -0.436
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.069
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 -0.70
Confidence Interval (2-Sided) 95%
-0.841 to -0.566
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.070
Estimation Comments
2. Secondary Outcome
Title Percentage of Patients With HbA1c <7% at Week 26
Description 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

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 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. 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. 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.
Measure Participants 232 239 229
Number [Percentage of patients]
28.0
47.7
58.5
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 2.96
Confidence Interval () 95%
1.93 to 4.56
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 4.48
Confidence Interval () 95%
2.89 to 6.95
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
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 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. 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. 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.
Measure Participants 231 239 229
Least Squares Mean (Standard Error) [mg/dL]
7.39
(2.875)
-18.1
(2.860)
-20.3
(2.920)
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 -25.5
Confidence Interval (2-Sided) 95%
-31.68 to -19.32
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.147
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 -27.7
Confidence Interval (2-Sided) 95%
-33.97 to -21.49
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.179
Estimation Comments
4. Secondary Outcome
Title Percent Change in Body Weight From Baseline to Week 26
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 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 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. 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. 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.
Measure Participants 234 240 229
Least Squares Mean (Standard Error) [Percent change]
-0.1
(0.3)
-2.4
(0.3)
-3.1
(0.3)
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 <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-2.8 to -1.7
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 -3.0
Confidence Interval (2-Sided) 95%
-3.5 to -2.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.3
Estimation Comments
5. Secondary Outcome
Title 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
Description 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

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 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. 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. 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.
Measure Participants 50 56 60
Least Squares Mean (Standard Error) [kg]
-0.28
(0.336)
-1.87
(0.332)
-2.38
(0.323)
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 -1.59
Confidence Interval (2-Sided) 95%
-2.339 to -0.842
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.379
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 -2.10
Confidence Interval (2-Sided) 95%
-2.833 to -1.368
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.371
Estimation Comments
6. Secondary Outcome
Title 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
Description 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

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 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. 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. 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.
Measure Participants 50 56 60
Least Squares Mean (Standard Error) [Percent]
0.00
(0.270)
-1.03
(0.268)
-1.18
(0.261)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 100 mg
Comments Region percent total fat
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 -1.03
Confidence Interval (2-Sided) 95%
-1.633 to -0.428
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.305
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin 300 mg
Comments Region percent total fat
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 -1.18
Confidence Interval (2-Sided) 95%
-1.772 to -0.587
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.300
Estimation Comments
7. Secondary Outcome
Title 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
Description 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

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 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. 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. 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.
Measure Participants 50 56 60
Least Squares Mean (Standard Error) [Percent]
0.02
(0.280)
-1.04
(0.278)
-1.18
(0.270)
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 -1.05
Confidence Interval (2-Sided) 95%
-1.677 to -0.430
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.316
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 -1.20
Confidence Interval (2-Sided) 95%
-1.812 to -0.584
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.311
Estimation Comments
8. Secondary Outcome
Title Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
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 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. 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. 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.
Measure Participants 234 240 229
Least Squares Mean (Standard Error) [mmHg]
1.10
(1.039)
-3.52
(1.035)
-6.79
(1.056)
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 -4.63
Confidence Interval (2-Sided) 95%
-6.854 to -2.401
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.134
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 -7.89
Confidence Interval (2-Sided) 95%
-10.14 to -5.641
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.147
Estimation Comments
9. Secondary Outcome
Title Percent Change in Triglycerides From Baseline to Week 26
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 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 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. 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. 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.
Measure Participants 206 227 222
Least Squares Mean (Standard Error) [Percent change]
7.7
(3.4)
2.8
(3.3)
8.4
(3.4)
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 0.194
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-12.1 to 2.5
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.7
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 0.846
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-6.6 to 8.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.7
Estimation Comments
10. Secondary Outcome
Title Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
Description 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

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 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. 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. 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.
Measure Participants 206 225 222
Least Squares Mean (Standard Error) [Percent change]
1.5
(1.2)
6.8
(1.2)
6.2
(1.2)
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 5.3
Confidence Interval (2-Sided) 95%
2.6 to 7.9
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4
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 4.7
Confidence Interval (2-Sided) 95%
2.0 to 7.4
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4
Estimation Comments
11. Secondary Outcome
Title Percent Change in Lumbar Spine Bone Mineral Density (BMD) From Baseline to Week 26
Description 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

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 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. 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. 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.
Measure Participants 185 206 192
Least Squares Mean (Standard Error) [Percent change]
0.5
(0.3)
0.7
(0.3)
0.2
(0.3)
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.4 to 0.8
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.9 to 0.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.3
Estimation Comments
12. Secondary Outcome
Title Percent Change in Distal Forearm Bone Mineral Density (BMD) From Baseline to Week 26
Description 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

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 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. 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. 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.
Measure Participants 187 208 187
Least Squares Mean (Standard Error) [Percent change]
-0.5
(0.3)
-0.7
(0.3)
-0.8
(0.3)
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.9 to 0.4
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.0 to 0.3
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.3
Estimation Comments
13. Secondary Outcome
Title Percent Change in Femoral Neck Bone Mineral Density (BMD) From Baseline to Week 26
Description 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

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 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. 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. 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.
Measure Participants 183 209 190
Least Squares Mean (Standard Error) [Percent change]
-1.0
(0.3)
-0.7
(0.3)
-0.6
(0.3)
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.3 to 1.0
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.3 to 1.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.3
Estimation Comments
14. Secondary Outcome
Title Percent Change in Total Hip Bone Mineral Density (BMD) From Baseline to Week 26
Description 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

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 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. 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. 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.
Measure Participants 183 209 190
Least Squares Mean (Standard Error) [Percent change]
-0.5
(0.2)
-0.9
(0.2)
-1.0
(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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.8 to -0.0
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2
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
Comments
Method
Comments
Method of Estimation Estimation Parameter Least-Squares Mean Difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-0.9 to -0.1
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2
Estimation Comments

Adverse Events

Time Frame Adverse event data was collected for the duration of the study (104 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. MEDDRA 14.0 used for Week 26 results/ MEDDRA 16.0 used for Week 104 results.
Arm/Group Title Placebo: Baseline to Week 26 Canagliflozin 100 mg: Baseline to Week 26 Canagliflozin 300 mg: Baseline to Week 26 Placebo: Baseline to Week 104 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104
Arm/Group Description 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. Data are presented for Baseline to Week 26. 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. Data are presented for Baseline to Week 26. 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. Data are presented for Baseline to Week 26. 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. Data are presented for Baseline to Week 104. 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. Data are presented for Baseline to Week 104 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. Data are presented for Baseline to Week 104
All Cause Mortality
Placebo: Baseline to Week 26 Canagliflozin 100 mg: Baseline to Week 26 Canagliflozin 300 mg: Baseline to Week 26 Placebo: Baseline to Week 104 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104
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)
Serious Adverse Events
Placebo: Baseline to Week 26 Canagliflozin 100 mg: Baseline to Week 26 Canagliflozin 300 mg: Baseline to Week 26 Placebo: Baseline to Week 104 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104
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 12/237 (5.1%) 10/241 (4.1%) 8/236 (3.4%) 41/237 (17.3%) 40/241 (16.6%) 43/236 (18.2%)
Cardiac disorders
Angina pectoris 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 1/237 (0.4%) 1/241 (0.4%) 0/236 (0%)
Atrial fibrillation 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 2/237 (0.8%) 1/241 (0.4%) 3/236 (1.3%)
Bradycardia 0/237 (0%) 0/241 (0%) 1/236 (0.4%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Cardiac failure congestive 0/237 (0%) 0/241 (0%) 1/236 (0.4%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Coronary artery disease 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 3/237 (1.3%) 3/241 (1.2%) 3/236 (1.3%)
Myocardial infarction 2/237 (0.8%) 0/241 (0%) 1/236 (0.4%) 2/237 (0.8%) 1/241 (0.4%) 2/236 (0.8%)
Myocarditis 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Acute myocardial infarction 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 2/236 (0.8%)
Angina unstable 0/237 (0%) 0/241 (0%) 0/236 (0%) 2/237 (0.8%) 0/241 (0%) 2/236 (0.8%)
Intracardiac thrombus 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Sick sinus syndrome 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Eye disorders
Diplopia 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 0/236 (0%)
Gastrointestinal disorders
Haematochezia 0/237 (0%) 0/241 (0%) 1/236 (0.4%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Intestinal infarction 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Umbilical hernia, obstructive 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Abdominal hernia obstructive 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Abdominal pain upper 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Colitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Gastrointestinal angiodysplasia haemorrhagic 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Gastrointestinal haemorrhage 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Gastrooesophageal reflux disease 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Inguinal hernia, obstructive 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Intestinal obstruction 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 1/241 (0.4%) 1/236 (0.4%)
Lower gastrointestinal haemorrhage 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 2/236 (0.8%)
Pancreatitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Pouchitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Small intestinal obstruction 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
General disorders
Non-cardiac chest pain 0/237 (0%) 0/241 (0%) 0/236 (0%) 2/237 (0.8%) 1/241 (0.4%) 0/236 (0%)
Hepatobiliary disorders
Bile duct obstruction 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Cholecystitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 1/241 (0.4%) 0/236 (0%)
Cholecystitis acute 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Cholelithiasis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Immune system disorders
Drug hypersensitivity 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Infections and infestations
Pneumonia 0/237 (0%) 0/241 (0%) 2/236 (0.8%) 2/237 (0.8%) 0/241 (0%) 3/236 (1.3%)
Urinary tract infection 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 1/241 (0.4%) 0/236 (0%)
Urosepsis 2/237 (0.8%) 0/241 (0%) 0/236 (0%) 2/237 (0.8%) 0/241 (0%) 0/236 (0%)
Appendicitis perforated 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Cholecystitis infective 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 2/241 (0.8%) 0/236 (0%)
Gastroenteritis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Otitis media 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Sepsis 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 1/236 (0.4%)
Subcutaneous abscess 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Injury, poisoning and procedural complications
Ankle fracture 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 2/241 (0.8%) 0/236 (0%)
Cervical vertebral fracture 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Hand fracture 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Hip fracture 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Joint dislocation 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Laceration 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Meniscus injury 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Muscle rupture 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Procedural pain 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Investigations
Blood pressure increased 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Metabolism and nutrition disorders
Hypoglycaemia 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Diabetic ketoacidosis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Musculoskeletal and connective tissue disorders
Osteoarthritis 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 1/237 (0.4%) 1/241 (0.4%) 2/236 (0.8%)
Cartilage atrophy 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Cervical spinal stenosis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Foot deformity 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Muscular weakness 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Musculoskeletal chest pain 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 1/241 (0.4%) 0/236 (0%)
Spinal column stenosis 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchioloalveolar carcinoma 0/237 (0%) 0/241 (0%) 1/236 (0.4%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Metastases to central nervous system 0/237 (0%) 0/241 (0%) 1/236 (0.4%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Prostate cancer 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 2/241 (0.8%) 0/236 (0%)
Squamous cell carcinoma 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Adrenal adenoma 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Angiosarcoma 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Benign salivary gland neoplasm 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Breast cancer 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 2/236 (0.8%)
Colon cancer 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Hodgkin's disease 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Papillary thyroid cancer 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 2/236 (0.8%)
Thyroid neoplasm 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Nervous system disorders
Carotid artery stenosis 0/237 (0%) 0/241 (0%) 1/236 (0.4%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Cerebrovascular accident 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 3/241 (1.2%) 1/236 (0.4%)
Presyncope 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Cauda equina syndrome 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Hepatic encephalopathy 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Hypoaesthesia 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Hypoglycaemic coma 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Hypoglycaemic seizure 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Loss of consciousness 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Migraine with aura 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Syncope 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Transient ischaemic attack 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Psychiatric disorders
Post-traumatic stress disorder 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Renal and urinary disorders
Renal colic 1/237 (0.4%) 0/241 (0%) 0/236 (0%) 2/237 (0.8%) 0/241 (0%) 0/236 (0%)
Renal impairment 1/237 (0.4%) 0/241 (0%) 1/236 (0.4%) 1/237 (0.4%) 0/241 (0%) 1/236 (0.4%)
Calculus ureteric 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Nephrolithiasis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 3/241 (1.2%) 1/236 (0.4%)
Reproductive system and breast disorders
Balanoposthitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Benign prostatic hyperplasia 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Genital prolapse 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 2/241 (0.8%) 0/236 (0%)
Respiratory failure 0/237 (0%) 1/241 (0.4%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Asthma 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Hypoventilation 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Nasal septum deviation 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Pulmonary embolism 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Pulmonary fibrosis 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 0/241 (0%) 0/236 (0%)
Sinus polyp 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Skin and subcutaneous tissue disorders
Psoriasis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Vascular disorders
Deep vein thrombosis 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Embolism arterial 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 1/241 (0.4%) 0/236 (0%)
Haematoma 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Peripheral vascular disorder 0/237 (0%) 0/241 (0%) 0/236 (0%) 0/237 (0%) 0/241 (0%) 1/236 (0.4%)
Other (Not Including Serious) Adverse Events
Placebo: Baseline to Week 26 Canagliflozin 100 mg: Baseline to Week 26 Canagliflozin 300 mg: Baseline to Week 26 Placebo: Baseline to Week 104 Canagliflozin 100 mg: Baseline to Week 104 Canagliflozin 300 mg: Baseline to Week 104
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 99/237 (41.8%) 92/241 (38.2%) 98/236 (41.5%) 166/237 (70%) 169/241 (70.1%) 169/236 (71.6%)
Gastrointestinal disorders
Diarrhoea 14/237 (5.9%) 10/241 (4.1%) 11/236 (4.7%) 24/237 (10.1%) 14/241 (5.8%) 24/236 (10.2%)
Constipation 0/237 (0%) 0/241 (0%) 0/236 (0%) 8/237 (3.4%) 18/241 (7.5%) 13/236 (5.5%)
Nausea 0/237 (0%) 0/241 (0%) 0/236 (0%) 16/237 (6.8%) 11/241 (4.6%) 13/236 (5.5%)
General disorders
Oedema peripheral 0/237 (0%) 0/241 (0%) 0/236 (0%) 17/237 (7.2%) 6/241 (2.5%) 2/236 (0.8%)
Infections and infestations
Influenza 5/237 (2.1%) 14/241 (5.8%) 9/236 (3.8%) 18/237 (7.6%) 25/241 (10.4%) 18/236 (7.6%)
Nasopharyngitis 19/237 (8%) 23/241 (9.5%) 19/236 (8.1%) 36/237 (15.2%) 45/241 (18.7%) 44/236 (18.6%)
Upper respiratory tract infection 11/237 (4.6%) 13/241 (5.4%) 10/236 (4.2%) 29/237 (12.2%) 23/241 (9.5%) 25/236 (10.6%)
Urinary tract infection 9/237 (3.8%) 14/241 (5.8%) 17/236 (7.2%) 21/237 (8.9%) 32/241 (13.3%) 35/236 (14.8%)
Bronchitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 8/237 (3.4%) 15/241 (6.2%) 11/236 (4.7%)
Sinusitis 0/237 (0%) 0/241 (0%) 0/236 (0%) 13/237 (5.5%) 9/241 (3.7%) 6/236 (2.5%)
Vulvovaginal mycotic infection 0/237 (0%) 0/241 (0%) 0/236 (0%) 1/237 (0.4%) 13/241 (5.4%) 11/236 (4.7%)
Metabolism and nutrition disorders
Hypoglycaemia 34/237 (14.3%) 25/241 (10.4%) 23/236 (9.7%) 47/237 (19.8%) 37/241 (15.4%) 36/236 (15.3%)
Hyperglycaemia 0/237 (0%) 0/241 (0%) 0/236 (0%) 19/237 (8%) 6/241 (2.5%) 6/236 (2.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 12/237 (5.1%) 4/241 (1.7%) 5/236 (2.1%) 24/237 (10.1%) 21/241 (8.7%) 9/236 (3.8%)
Back pain 8/237 (3.4%) 6/241 (2.5%) 12/236 (5.1%) 19/237 (8%) 24/241 (10%) 28/236 (11.9%)
Muscle spasms 0/237 (0%) 0/241 (0%) 0/236 (0%) 13/237 (5.5%) 4/241 (1.7%) 6/236 (2.5%)
Pain in extremity 0/237 (0%) 0/241 (0%) 0/236 (0%) 11/237 (4.6%) 16/241 (6.6%) 11/236 (4.7%)
Nervous system disorders
Headache 15/237 (6.3%) 8/241 (3.3%) 13/236 (5.5%) 25/237 (10.5%) 14/241 (5.8%) 22/236 (9.3%)
Dizziness 0/237 (0%) 0/241 (0%) 0/236 (0%) 13/237 (5.5%) 9/241 (3.7%) 6/236 (2.5%)
Psychiatric disorders
Insomnia 0/237 (0%) 0/241 (0%) 0/236 (0%) 6/237 (2.5%) 5/241 (2.1%) 12/236 (5.1%)
Renal and urinary disorders
Pollakiuria 6/237 (2.5%) 6/241 (2.5%) 12/236 (5.1%) 10/237 (4.2%) 11/241 (4.6%) 15/236 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough 0/237 (0%) 0/241 (0%) 0/236 (0%) 22/237 (9.3%) 17/241 (7.1%) 18/236 (7.6%)
Oropharyngeal pain 0/237 (0%) 0/241 (0%) 0/236 (0%) 15/237 (6.3%) 11/241 (4.6%) 7/236 (3%)
Vascular disorders
Hypertension 0/237 (0%) 0/241 (0%) 0/236 (0%) 12/237 (5.1%) 5/241 (2.1%) 7/236 (3%)

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
Email ClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01106651
Other Study ID Numbers:
  • CR017014
  • 28431754DIA3010
First Posted:
Apr 20, 2010
Last Update Posted:
Nov 4, 2014
Last Verified:
Oct 1, 2014