The CANTATA-MSU Trial (CANagliflozin Treatment And Trial... | NCT01106625 | Trialant
NCT01106625
Sponsor
Janssen Research & Development, LLC
Status
Completed
Last Update Posted
Jun 20, 2013Estimated
Enrollment
469Actual
Phase
Phase 3
Conditions
Diabetes Mellitus, Type 2
Interventions
Canagliflozin
Placebo
Metformin
Sulphonylruea
Countries
United States
Australia
Belgium
France
Guatemala
Hungary
Israel
Mexico
Puerto Rico
Russia
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT01106625
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CR017005
Secondary IDs
ID
Type
Description
Link
28431754DIA3002
Other Identifier
Janssen Research & Development, LLC
Brief Title
The CANTATA-MSU Trial (CANagliflozin Treatment And Trial Analysis - Metformin and SUlphonylurea)
Official Title
A Randomized, Double-Blind, Placebo-Controlled, 3-Arm, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin and Sulphonylurea Therapy
Acronym
Not provided
Organization
Janssen Research & Development, LLCINDUSTRY
Status Module
Record Verification Date
Jun 2013
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 2010
Primary Completion Date
Sep 2011Actual
Completion Date
Apr 2012Actual
First Submitted Date
Apr 1, 2010
First Submission Date that Met QC Criteria
Apr 19, 2010
First Posted Date
Apr 20, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 10, 2013
Results First Submitted that Met QC Criteria
Apr 10, 2013
Results First Posted Date
May 29, 2013Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 30, 2012
Certification/Extension First Submitted that Passed QC Review
Jun 29, 2012
Certification/Extension First Posted Date
Jul 2, 2012Estimated
Last Update Submitted Date
Jun 12, 2013
Last Update Posted Date
Jun 20, 2013Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Janssen Research & Development, LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control.
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 with metformin and sulphonylurea to control their diabetes. Approximately 450 patients with T2DM who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control will receive once daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 52 weeks (includes 26 weeks of double-blind treatment followed by a 26-week extension period). In addition, all patients will take protocol-specified stable doses of metformin and sulphonylurea for the duration of the study. Patients will participate in the study for approximately 59 to 72 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with insulin (rescue therapy) consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 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 to assess 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 52 weeks.
Conditions Module
Conditions
Diabetes Mellitus, Type 2
Keywords
Canagliflozin
Placebo
Metformin
Sulphonylurea
Hemoglobin A1c
Type 2 diabetes mellitus
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
469Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Canagliflozin 100 mg
Experimental
Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Drug: Canagliflozin
Drug: Metformin
Drug: Sulphonylruea
Canagliflozin 300 mg
Experimental
Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Drug: Canagliflozin
Drug: Metformin
Drug: Sulphonylruea
Placebo
Placebo Comparator
Each patient will receive matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Drug: Placebo
Drug: Metformin
Drug: Sulphonylruea
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Canagliflozin
Drug
One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Canagliflozin 100 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Day 1 (Baseline) and Week 26
Secondary Outcomes
Measure
Description
Time Frame
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.
Week 26
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
All patients must have a diagnosis of T2DM and be currently treated with metformin and sulphonylurea
Patients in the study must have a HbA1c between >=7 and <=10.5%
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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
80 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Janssen Research & Development, LLC C. Clinical Trial
Cai J, Delahanty LM, Akapame S, Slee A, Traina S. Impact of Canagliflozin Treatment on Health-Related Quality of Life among People with Type 2 Diabetes Mellitus: A Pooled Analysis of Patient-Reported Outcomes from Randomized Controlled Trials. Patient. 2018 Jun;11(3):341-352. doi: 10.1007/s40271-017-0290-4.
A total of 469 patients were randomly allocated to the 3 treatment arms in the study. All 469 patients received at least 1 dose of study drug and were included in the modified intent-to-treat analysis set (used for the week 26 efficacy analyses). All 469 patients were included in the week 26 and week 52 safety analysis sets.
Recruitment Details
This study evaluated the efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus with inadequate control despite treatment with metformin and sulphonylurea therapy. The study was conducted between 07 April 2010 and 17 April 2012 and recruited patients from 85 study centers in 11 countries worldwide.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
FG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Periods
Title
Milestones
Reasons Not Completed
Core Period: Baseline to Week 26
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Germany
Ireland
Portugal
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantCare ProviderInvestigator
Canagliflozin 300 mg
Placebo
Drug
One matching placebo capsule orally once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Placebo
Metformin
Drug
The patient's stable dose of background metformin therapy should be continued throughout the study.
Canagliflozin 100 mg
Canagliflozin 300 mg
Placebo
Sulphonylruea
Drug
The patient's stable dose of background sulphonylurea therapy should be continued throughout the study.
Canagliflozin 100 mg
Canagliflozin 300 mg
Placebo
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.
Day 1 (Baseline) and Week 26
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 percent change.
Day 1 (Baseline) and Week 26
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.
Day 1 (Baseline) and Week 26
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 percent change.
Day 1 (Baseline) and Week 26
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 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
Davies MJ, Merton K, Vijapurkar U, Yee J, Qiu R. Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data. Cardiovasc Diabetol. 2017 Mar 21;16(1):40. doi: 10.1186/s12933-017-0517-7.
Pfeifer M, Townsend RR, Davies MJ, Vijapurkar U, Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol. 2017 Feb 27;16(1):29. doi: 10.1186/s12933-017-0511-0.
Gilbert RE, Mende C, Vijapurkar U, Sha S, Davies MJ, Desai M. Effects of Canagliflozin on Serum Magnesium in Patients With Type 2 Diabetes Mellitus: A Post Hoc Analysis of Randomized Controlled Trials. Diabetes Ther. 2017 Apr;8(2):451-458. doi: 10.1007/s13300-017-0232-0. Epub 2017 Feb 14.
Qiu R, Balis D, Xie J, Davies MJ, Desai M, Meininger G. Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. Curr Med Res Opin. 2017 Mar;33(3):553-562. doi: 10.1080/03007995.2016.1271780. Epub 2017 Jan 4.
John M, Cerdas S, Violante R, Deerochanawong C, Hassanein M, Slee A, Canovatchel W, Hamilton G. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates. Int J Clin Pract. 2016 Sep;70(9):775-85. doi: 10.1111/ijcp.12868.
Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.
Lavalle-Gonzalez FJ, Eliaschewitz FG, Cerdas S, Chacon Mdel P, Tong C, Alba M. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America. Curr Med Res Opin. 2016;32(3):427-39. doi: 10.1185/03007995.2015.1121865. Epub 2016 Jan 14.
Blonde L, Woo V, Mathieu C, Yee J, Vijapurkar U, Canovatchel W, Meininger G. Achievement of treatment goals with canagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of randomized controlled trials. Curr Med Res Opin. 2015 Nov;31(11):1993-2000. doi: 10.1185/03007995.2015.1082991. Epub 2015 Sep 28.
Gavin JR 3rd, Davies MJ, Davies M, Vijapurkar U, Alba M, Meininger G. The efficacy and safety of canagliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31(9):1693-702. doi: 10.1185/03007995.2015.1067192. Epub 2015 Sep 4.
Cefalu WT, Stenlof K, Leiter LA, Wilding JP, Blonde L, Polidori D, Xie J, Sullivan D, Usiskin K, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes. Diabetologia. 2015 Jun;58(6):1183-7. doi: 10.1007/s00125-015-3547-2. Epub 2015 Mar 27.
Weir MR, Januszewicz A, Gilbert RE, Vijapurkar U, Kline I, Fung A, Meininger G. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2014 Dec;16(12):875-82. doi: 10.1111/jch.12425. Epub 2014 Oct 20.
Usiskin K, Kline I, Fung A, Mayer C, Meininger G. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. Postgrad Med. 2014 May;126(3):16-34. doi: 10.3810/pgm.2014.05.2753.
Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.
Sinclair A, Bode B, Harris S, Vijapurkar U, Mayer C, Fung A, Shaw W, Usiskin K, Desai M, Meininger G. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. BMC Endocr Disord. 2014 Apr 18;14:37. doi: 10.1186/1472-6823-14-37.
Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes. Diabetologia. 2014 May;57(5):891-901. doi: 10.1007/s00125-014-3196-x. Epub 2014 Mar 1.
Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.
FG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
FG000156 subjects
FG001157 subjects
FG002156 subjects
COMPLETED
FG000123 subjects
FG001129 subjects
FG002129 subjects
NOT COMPLETED
FG00033 subjects
FG00128 subjects
FG00227 subjects
Type
Comment
Reasons
Adverse Event
FG0006 subjects
FG0018 subjects
FG0028 subjects
Lost to Follow-up
FG0005 subjects
FG0010 subjects
FG0024 subjects
Physician Decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
Protocol Violation
FG0002 subjects
FG0011 subjects
FG0023 subjects
Withdrawal by Subject
FG0006 subjects
FG0019 subjects
FG0027 subjects
Unable to take rescue therapy
FG0004 subjects
FG0011 subjects
FG0020 subjects
Creatinine, or eGFR withdrawal criteria
FG0000 subjects
FG0011 subjects
FG0021 subjects
Noncompliance with study drug
FG0001 subjects
FG0011 subjects
FG0020 subjects
Other
FG0008 subjects
FG0017 subjects
FG0024 subjects
Extension Period: Week 26 to Week 52
Type
Comment
Milestone Data
STARTED
FG000119 subjects4 pts discontinued last day of core: physician decision (1), noncompliance (1), not specified (2).
FG001127 subjects2 pts discontinued last day of core: adverse event (1), not specified (1).
FG002128 subjects1 pt discontinued last day of core: withdrawal by subject (1).
COMPLETED
FG00090 subjects
FG001109 subjects
FG002111 subjects
NOT COMPLETED
FG00029 subjects
FG00118 subjects
FG00217 subjects
Type
Comment
Reasons
Adverse Event
FG0002 subjects
FG0012 subjects
FG0023 subjects
Lost to Follow-up
FG000
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
BG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
BG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000156
BG001157
BG002156
BG003469
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Age Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00056.7± 8.36
BG00157.3± 10.47
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00080
BG00181
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
AUSTRALIA
Title
Measurements
BG0003
BG0016
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
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.
Posted
Least Squares Mean
Standard Error
Percent
Day 1 (Baseline) and Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Units
Counts
Participants
OG000150
OG001155
OG002152
Title
Denominators
Categories
Title
Measurements
OG000-0.13± 0.075
OG001-0.85± 0.075
OG002-1.06± 0.076
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
<0.001
Least-Squares Mean Difference
-0.71
Standard Error of the Mean
0.097
2-Sided
95
-0.904
-0.524
No
Superiority or Other
OG000
OG002
ANCOVA
<0.001
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.
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.
Posted
Number
Percentage of patients
Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
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.
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.
Posted
Least Squares Mean
Standard Error
mg/dL
Day 1 (Baseline) and Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
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 percent change.
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.
Posted
Least Squares Mean
Standard Error
Percent change
Day 1 (Baseline) and Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
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.
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.
Posted
Least Squares Mean
Standard Error
mmHg
Day 1 (Baseline) and Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
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 percent change.
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.
Posted
Least Squares Mean
Standard Error
Percent change
Day 1 (Baseline) and Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
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 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
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.
Posted
Least Squares Mean
Standard Error
Percent change
Day 1 (Baseline) and Week 26
ID
Title
Description
OG000
Placebo
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG001
Canagliflozin 100 mg
Each patient received 100 mg of canagliflozin once daily for for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
OG002
Canagliflozin 300 mg
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.
Time Frame
Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks.
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo: Baseline to Week 26
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea. Data are presented for Baseline to Week 26.
9
156
31
156
EG001
Canagliflozin 100 mg: Baseline to Week 26
Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea. Data are presented for Baseline to Week 26.
5
157
42
157
EG002
Canagliflozin 300 mg: Baseline to Week 26
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea. Data are presented for Baseline to Week 26.
6
156
38
156
EG003
Placebo: Baseline to Week 52
Each patient received matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea. Data are presented for Baseline to Week 52.
13
156
52
156
EG004
Canagliflozin 100 mg: Baseline to Week 52
Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea. Data are presented for Baseline to Week 52.
7
157
63
157
EG005
Canagliflozin 300 mg: Baseline to Week 52
Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea. Data are presented for Baseline to Week 52.
8
156
54
156
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Angina pectoris
Cardiac disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG0031 affected156 at risk
EG004
Chest pain
General disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Uterine enlargement
Reproductive system and breast disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Uterine prolapse
Reproductive system and breast disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Atrial fibrillation
Cardiac disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Coronary artery stenosis
Cardiac disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Myocardial infarction
Cardiac disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Mechanical ileus
Gastrointestinal disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Ulcer haemorrhage
General disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Biliary dyskinesia
Hepatobiliary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Cholecystitis chronic
Hepatobiliary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Diverticulitis
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Gangrene
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Lobar pneumonia
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Pneumonia
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Scrotal gangrene
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Urinary tract infection
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Urosepsis
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Wound complication
Injury, poisoning and procedural complications
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Spinal osteoarthritis
Musculoskeletal and connective tissue disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Colon cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Calculus ureteric
Renal and urinary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Hydronephrosis
Renal and urinary disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0011 affected157 at risk
EG0020 affected156 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Deep vein thrombosis
Vascular disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0021 affected156 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0001 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Influenza
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG0038 affected156 at risk
EG004
Sinusitis
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Headache
Nervous system disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0000 affected156 at risk
EG0010 affected157 at risk
EG0020 affected156 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0005 affected156 at risk
EG0015 affected157 at risk
EG00210 affected156 at risk
EG003
Nasopharyngitis
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0004 affected156 at risk
EG0016 affected157 at risk
EG0028 affected156 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG00010 affected156 at risk
EG00117 affected157 at risk
EG0026 affected156 at risk
EG003
Urinary tract infection
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0008 affected156 at risk
EG0019 affected157 at risk
EG0027 affected156 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0002 affected156 at risk
EG0018 affected157 at risk
EG0028 affected156 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MEDDRA 14.0/15.0
Non-systematic Assessment
Source vocabulary is MEDDRA 14.0 for Week 26 and MEDDRA 15.0 for Week 52.
EG0006 affected156 at risk
EG00111 affected157 at risk
EG0029 affected156 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Point of Contact
Title
Organization
Phone
Extension
Email
Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise