The CANTATA-D Trial (CANagliflozin Treatment and Trial An... | NCT01106677

NCT01106677

ID	Type	Description	Link
28431754DIA3006	Other Identifier	Janssen Research & Development, LLC

Status Module

Description Module

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 nor the study doctor will know the identity of assigned study drug), placebo- and active-controlled, parallel-group, 4-arm (4 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) and an active-control (sitagliptin 100 mg, an antihyperglycemic agent) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin Immediate Release (IR) to control their diabetes. Approximately 1,260 patients with T2DM who are receiving treatment with metformin IR and have inadequate glycemic (blood sugar) will receive once-daily treatment with canagliflozin (100 mg or 300 mg), sitagliptin 100 mg, or placebo capsules for 26 weeks (Period I) followed by another 26-weeks where patients treated with canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg will continue treatment for an additional 26 weeks and patients treated with placebo will be switched to active double-blind treatment with sitagliptin 100 mg capsules administered once-daily for 26 weeks (Period II). In addition, all patients will take protocol specified stable doses of metformin IR along with assigned study drug for the duration of the study. Patients will participate in the study for approximately 59 to 71 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, metformin IR, and reinforcement with diet and exercise, the patient will receive treatment with glimepiride (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 sign 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. Patients will take single-blind placebo for 2 weeks before randomization. After randomization, patients in the study will take double-blind canagliflozin (100 mg or 300 mg) or sitagliptin 100 mg for 52 weeks OR placebo for 26 weeks switched to double-blind treatment with sitaliptin 100 mg for 26 weeks.

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 immediate release.	Drug: Canagliflozin Drug: Metformin immediate release
Canagliflozin 300 mg	Experimental	Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Drug: Canagliflozin Drug: Metformin immediate release
Sitagliptin 100 mg	Active Comparator	Each patient will receive 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.	Drug: Sitagliptin Drug: Metformin immediate release
Placebo/Sitagliptin	Other	Each patient will receive matching placebo once daily for 26 weeks and will then switch from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin will be given with protocol-specified doses of metformin immediate release.	Drug: Placebo Drug: Sitagliptin Drug: Metformin immediate release

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	One matching placebo capsule orally (by mouth) once daily for 26 weeks with protocol-specified doses of metformin immediate release.	Placebo/Sitagliptin

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 or sitagliptin 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 between each canagliflozin or sitagliptin group and placebo.	Week 26
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26

Eligibility Module

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
29313267	Derived	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.
28327140	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
FG001	Canagliflozin 100 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
BG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
BG002	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
BG003	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
BG004	Total	Total of all reporting groups

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
	BG00055.3± 9.76 BG00155.5± 9.38 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00089 BG001194 BG002

Region Enroll

Number

participants

Title

Denominators

Categories

ARGENTINA

Title	Measurements
	BG0008 BG0019 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 or sitagliptin 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/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG003	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Units	Counts
Participants	OG000181 OG001365 OG002360 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.17± 0.060 OG001-0.79± 0.044 OG002-0.94± 0.044 OG003

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	-0.62	Standard Error of the Mean	0.071	2-Sided	95	-0.758	-0.481				Yes	Non-Inferiority or Equivalence	Power calculation: assuming a difference between canagliflozin and placebo of 0.5% and a common standard deviation of 1.0%, and using a 2-sample, 1-sided t-test with a Type I error rate of 0.05, it was estimated that 86 subjects per group would provide 90% power to demonstrate superiority of canagliflozin over placebo.

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 between each canagliflozin or sitagliptin group and placebo.

Posted

Number

Percentage of patients

Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

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 or sitagliptin group minus placebo) in the LS mean change.

Posted

Least Squares Mean

Standard Error

mg/dL

Day 1 (Baseline) and Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg

Secondary

Change in 2-hour Post-prandial Glucose From Baseline to Week 26

The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the LS mean change.

Posted

Least Squares Mean

Standard Error

mg/dL

Day 1 (Baseline) and Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg

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 or sitagliptin group minus placebo) in the LS mean percent change.

Posted

Least Squares Mean

Standard Error

Percent change

Day 1 (Baseline) and Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg

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 or sitagliptin group minus placebo) in the LS mean change.

Posted

Least Squares Mean

Standard Error

mmHg

Day 1 (Baseline) and Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg

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 or sitagliptin group minus placebo) in the LS mean percent change.

Posted

Least Squares Mean

Standard Error

Percent change

Day 1 (Baseline) and Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg

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 or sitagliptin group minus placebo) in the LS mean percent change.

Posted

Least Squares Mean

Standard Error

Percent change

Day 1 (Baseline) and Week 26

ID	Title	Description
OG000	Placebo/Sitagliptin	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Canagliflozin 300 mg

Secondary

Change in HbA1c From Baseline to Week 52

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) 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 52 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 52

ID	Title	Description
OG000	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Secondary

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.

Posted

Least Squares Mean

Standard Error

mg/dL

Day 1 (Baseline) and Week 52

ID	Title	Description
OG000	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Secondary

Percent Change in Body Weight From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.

Posted

Least Squares Mean

Standard Error

Percent change

Day 1 (Baseline) and Week 52

ID	Title	Description
OG000	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Secondary

Change in Systolic Blood Pressure (SBP) From Baseline to Week 52

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean change.

Posted

Least Squares Mean

Standard Error

mmHg

Day 1 (Baseline) and Week 52

ID	Title	Description
OG000	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Secondary

Percent Change in Triglycerides From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.

Posted

Least Squares Mean

Standard Error

Percent change

Day 1 (Baseline) and Week 52

ID	Title	Description
OG000	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Secondary

Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 52

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 52 for each active treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus sitagliptin) in the LS mean percent change.

Posted

Least Squares Mean

Standard Error

Percent change

Day 1 (Baseline) and Week 52

ID	Title	Description
OG000	Canagliflozin 100 mg	Each patient received 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG001	Canagliflozin 300 mg	Each patient received 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin immediate release.
OG002	Sitagliptin 100 mg	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo/Sitagliptin: Baseline to Week 26	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 26.	4	183	31	183
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 immediate release. Data are presented for Baseline to Week 26.	12	368	55	368
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 immediate release. Data are presented for Baseline to Week 26.	10	367	45	367
EG003	Sitagliptin 100 mg: Baseline to Week 26	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 26.	8	366	42	366
EG004	Placebo/Sitagliptin: Baseline to Week 52	Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Placebo and sitagliptin were given with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 52.	7	183	55	183
EG005	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 immediate release. Data are presented for Baseline to Week 52.	15	368	108	368
EG006	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 immediate release. Data are presented for Baseline to Week 52.	12	367	101	367
EG007	Sitagliptin 100mg: Baseline to Week 52	Each patient received 100 mg of sitagliptin once daily for 52 weeks with protocol-specified doses of metformin immediate release. Data are presented for Baseline to Week 52.	18	366	109	366

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Acute coronary syndrome	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG0030 affected366 at risk EG004
Angina unstable	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Coronary artery disease	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Stress cardiomyopathy	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Supraventricular tachycardia	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Vertigo	Ear and labyrinth 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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Cataract nuclear	Eye 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. NOTE: event was reassessed as non-serious in the Week 52 study report.	EG0000 affected183 at risk EG0010 affected368 at risk EG0021 affected367 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. In the Week 26 study report, this event was coded as "abdominal pain"; it was subsequently re-coded in the Week 52 study report as "abdominal hernia".	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Constipation	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Inguinal hernia	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 affected183 at risk EG0011 affected368 at risk EG0021 affected367 at risk EG003
Umbilical hernia	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.	EG0000 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Hernia obstructive	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. In the Week 26 study report, this event was coded as "hernia obstructive"; it was subsequently re-coded in the Week 52 study report as "incisional hernia, obstructive".	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Cholangitis	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Cholecystitis acute	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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Cellulitis	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Gastroenteritis	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Pyothorax	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. In the Week 26 study report, this event was coded as "pyothorax"; it was subsequently re-coded in the Week 52 study report as "infectious pleural effusion".	EG0000 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Sepsis	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Subcutaneous abscess	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Burns second degree	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Cervical vertebral 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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
Incisional hernia	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.	EG0001 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Plantar fasciitis	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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Spinal column stenosis	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Breast cancer in situ	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Gastric 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Malignant mesenchymoma	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Meningioma	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Brain oedema	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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Coma	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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Ischaemic stroke	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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Transient ischaemic attack	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 affected183 at risk EG0011 affected368 at risk EG0020 affected367 at risk EG003
High risk pregnancy	Pregnancy, puerperium and perinatal conditions	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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Asthma	Respiratory, thoracic and mediastinal 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Arterial 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 affected183 at risk EG0010 affected368 at risk EG0021 affected367 at risk EG003
Hypertensive crisis	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Acute 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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Cardiac arrest	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Cardiomyopathy	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Abdominal hernia	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. In the Week 26 study report, this event was coded as "abdominal pain"; it was subsequently re-coded in the Week 52 study report as "abdominal hernia".	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Diverticulum	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Dengue fever	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Infectious pleural effusion	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. In the Week 26 study report, this event was coded as "pyothorax"; it was subsequently re-coded in the Week 52 study report as "infectious pleural effusion".	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Septic shock	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Incisional hernia, obstructive	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. In the Week 26 study report, this event was coded as "hernia obstructive"; it was subsequently re-coded in the Week 52 study report as "incisional hernia, obstructive".	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Multiple drug overdose	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Thermal burn	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Intervertebral disc protrusion	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Bronchial carcinoma	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Colorectal 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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Large cell lung cancer stage III	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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Prostate 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.	EG0000 affected183 at risk EG0010 affected368 at risk EG0020 affected367 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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Trigeminal neuralgia	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003
Renal failure acute	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 affected183 at risk EG0010 affected368 at risk EG0020 affected367 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
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.	EG00012 affected183 at risk EG00112 affected368 at risk EG00218 affected367 at risk EG00316 affected366 at risk EG004
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.	EG00013 affected183 at risk EG00115 affected368 at risk EG00210 affected367 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.	EG00012 affected183 at risk EG00112 affected368 at risk EG00210 affected367 at risk EG003
Pollakiuria	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.	EG0001 affected183 at risk EG00121 affected368 at risk EG00210 affected367 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.	EG0006 affected183 at risk EG0015 affected368 at risk EG00218 affected367 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.	EG0004 affected183 at risk EG00118 affected368 at risk EG00213 affected367 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.	EG0009 affected183 at risk EG0017 affected368 at risk EG0024 affected367 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.	EG0006 affected183 at risk EG0018 affected368 at risk EG00212 affected367 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Little Rock	Arkansas		United States

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D013876	Thiophenes
D013457	Sulfur Compounds
D009930	Organic Chemicals
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005960	Glucosides
D006027	Glycosides
D002241	Carbohydrates
D014230	Triazoles
D001393	Azoles
D011719	Pyrazines
D001645	Biguanides
D006146	Guanidines
D000578	Amidines

ID	Term
D000068896	Canagliflozin
D000068900	Sitagliptin Phosphate
D008687	Metformin