A Efficacy, Safety, and Tolerability Study of Canagliflozin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Alone or in Combination With a Sulphonylurea

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01381900
• Collaborator: (none)
• Enrollment: 678
• Locations: 25
• Arms: 3
• Duration (Months): 15
• Patients Per Site: 27.1
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety, tolerability, and efficacy of the addition of canagliflozin relative to the addition of placebo in patients with inadequate glycemic control on metformin alone or in combination with a sulphonylurea.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Placebo; Drug: Canagliflozin 100mg; Drug: Canagliflozin 300mg; Drug: Metformin; Drug: Sulphonylurea	Phase 3

Detailed Description

This is a double-blind (neither study staff or the patient will know the identity of the treatment assigned) study of canagliflozin where Chinese and other Asian adult patients with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic control on metformin alone or in combination with a sulphonylurea (SU) will be randomized (assigned to 1 of 3 treatments by chance) to receive the addition of treatment with canagliflozin 100 mg once daily, canagliflozin 300 mg once daily, or matching placebo capsules (placebo is a treatment identical in appearance to canagliflozin but does not contain active drug). All patients will take orally (by mouth) 1 single-blind placebo capsule once daily before the first meal of the day for up to 2 weeks (last dose of single-blind placebo to be taken the day before the baseline (Day 1) visit. On Day 1, patients will take orally, once daily 1 capsule of canagliflozin 100 mg, canagliflozin 300 mg, or placebo before the first meal of the day for up to 18 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 678 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, 18-Week 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 Alone or in Combination With a Sulphonylurea
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canagliflozin 100mg Each participant will receive 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Drug: Canagliflozin 100mg; Type=1, unit=mg, number=100, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).; Drug: Metformin; The participant's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Sulphonylurea; The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.
Experimental: Canagliflozin 300mg Each participant will receive 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Drug: Canagliflozin 300mg; Type=1, unit=mg, number=300, form=capsule, route=oral use. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).; Drug: Metformin; The participant's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Sulphonylurea; The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.
Placebo Comparator: Placebo Each participant will receive matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Drug: Placebo; Form=capsule, route=oral administration. One capsule once daily for up to 18 weeks after completing a single-blind placebo run-in period (1 placebo capsule once daily for up to 2 weeks).; Drug: Metformin; The participant's stable dose of background therapy of metformin should be continued throughout the study.; Drug: Sulphonylurea; The participant's stable dose of background therapy of metformin plus sulphonylurea should be continued throughout the study.

Outcome Measures

Primary Outcome Measures

1. Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 18 [Day 1 (Baseline) and Week 18]

   The table below shows the least-squares (LS) mean change in HbA1c from baseline to Week 18 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. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18 [Day 1 (Baseline) and Week 18]

   The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

2. Percent Change in Body Weight From Baseline to Week 18 [Day 1 (Baseline) and Week 18]

   The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

3. Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <7% at Week 18 [Day 1 (Baseline) and Week 18]

   The table below shows the percentage of patients with HbA1c <7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.

4. Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18 [Day 1 (Baseline) and Week 18]

   The table below shows the percentage of patients with HbA1c <6.5% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with T2DM with inadequate glycemic control on metformin monotherapy or on metformin in combination with an SU at protocol-specified doses and having HbA1c

=7.0% and <=10.5% at Week -2 are eligible for enrollment in the study.

Exclusion Criteria:

• History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy

• Has repeated (ie, 2 or more over a 1-week period) fasting plasma glucose (FPG) and/or fasting self-monitored blood glucose (SMBG) measurements >=270 mg/dL (15 mmol/L) during the pre-treatment phase, despite reinforcement of diet and exercise counseling

• History of a severe hypoglycemic episode within 6 months before screening

• History of or current illness considered to be clinically significant by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Baotou		China
2		Beijing		China
3		Changchun		China
4		Changsha		China
5		Chengdu		China
6		Chongqing		China
7		Guangzhou		China
8		Hangzhou		China
9		Harbin		China
10		Nanchang		China
11		Nanjing		China
12		Nanning		China
13		Shanghai		China
14		Shenyang		China
15		Shiyan		China
16		Siping		China
17		Su Zhou		China
18		Tianjin		China
19		Wuxi		China
20		Xi'An		China
21		Kota Bharu		Malaysia
22		Pulau Pinang		Malaysia
23		Selangor		Malaysia
24		Hanoi		Vietnam
25		Ho Chi Minh		Vietnam

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: NCT01381900
• Other Study ID Numbers: CR018541; 28431754DIA3014
• First Posted: Jun 27, 2011
• Last Update Posted: May 9, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Janssen Research & Development, LLC: Canagliflozin; Placebo; Type 2 diabetes mellitus
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Canagliflozin

Study Results

Participant Flow

Recruitment Details	This study evaluated the efficacy and safety of canagliflozin in Asian participants with type 2 diabetes mellitus who had inadequate glycemic control on a maximally effective or tolerated dose of metformin alone or metformin plus sulphonylurea (SU). It was conducted between 30 June 2011 and 21 December 2012 and recruited patients from 36 sites.
Pre-assignment Detail	The study had two background treatment strata: 331 participants in the metformin alone stratum and 347 in the metformin plus SU. In total, 678 participants were randomly allocated to the 3 treatment arms, 676 received at least 1 dose of study drug and were included in the modified intent-to-treat (mITT) analysis set and the safety analysis set.

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Period Title: Overall Study
STARTED	226	223	227
COMPLETED	217	214	215
NOT COMPLETED	9	9	12

Baseline Characteristics

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg	Total
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Total of all reporting groups
Overall Participants	226	223	227	676
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	184 81.4%	187 83.9%	186 81.9%	557 82.4%
>=65 years	42 18.6%	36 16.1%	41 18.1%	119 17.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.8 (9.35)	56.5 (8.25)	56.4 (9.21)	56.3 (8.94)
Sex: Female, Male (Count of Participants)
Female	101 44.7%	99 44.4%	114 50.2%	314 46.4%
Male	125 55.3%	124 55.6%	113 49.8%	362 53.6%
Region Enroll (participants) [Number]
China	213 94.2%	210 94.2%	213 93.8%	636 94.1%
Malaysia	3 1.3%	5 2.2%	4 1.8%	12 1.8%
Vietnam	10 4.4%	8 3.6%	10 4.4%	28 4.1%

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated Hemoglobin (HbA1c) From Baseline to Week 18
Description	The table below shows the least-squares (LS) mean change in HbA1c from baseline to Week 18 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 18

Outcome Measure Data

Analysis Population Description

Analysis used overall mITT analysis set (all randomized patients who received at least 1 dose of double-blind study drug). Last-observation-carried-forward method used for missing Week 18 values. Table includes only participants with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Measure Participants	226	223	227
Least Squares Mean (Standard Error) [Percent]	-0.47 (0.096)	-0.97 (0.095)	-1.06 (0.095)

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	-0.51
	Confidence Interval	(2-Sided) 95%; -0.644 to -0.367
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.071
	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	-0.59
	Confidence Interval	(2-Sided) 95%; -0.731 to -0.453
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.071
	Estimation Comments

2. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 18
Description	The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 18 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 18

Outcome Measure Data

Analysis Population Description

Analysis used overall mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 18 values. Table includes only participants with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Measure Participants	226	223	227
Least Squares Mean (Standard Error) [mg/dL]	-0.40 (0.237)	-1.44 (0.236)	-1.83 (0.235)

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	-1.03
	Confidence Interval	(2-Sided) 95%; -1.375 to -0.694
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.173
	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	-1.43
	Confidence Interval	(2-Sided) 95%; -1.769 to -1.089
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.173
	Estimation Comments

3. Secondary Outcome

Title	Percent Change in Body Weight From Baseline to Week 18
Description	The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 18 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.
Time Frame	Day 1 (Baseline) and Week 18

Outcome Measure Data

Analysis Population Description

Analysis used overall mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 18 values. Table includes only participants with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Measure Participants	226	223	227
Least Squares Mean (Standard Error) [Pecent change]	-0.8 (0.4)	-2.9 (0.4)	-3.1 (0.4)

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	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-Squares Mean Difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -2.7 to -1.6
	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	-2.3
	Confidence Interval	(2-Sided) 95%; -2.9 to -1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <7% at Week 18
Description	The table below shows the percentage of patients with HbA1c <7% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
Time Frame	Day 1 (Baseline) and Week 18

Outcome Measure Data

Analysis Population Description

Analysis used overall mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 18 values. Table includes only participants with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Measure Participants	226	223	227
Number [Percentage of patients]	27.8	49.1	52.9

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	Odds Ratio (OR)
	Estimated Value	3.26
	Confidence Interval	(2-Sided) 95%; 2.09 to 5.09
	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
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.99
	Confidence Interval	(2-Sided) 95%; 2.55 to 6.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Patients With Glycosylated Hemoglobin (HbA1c) <6.5% at Week 18
Description	The table below shows the percentage of patients with HbA1c <6.5% at Week 18 in each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.
Time Frame	Day 1 (Baseline) and Week 18

Outcome Measure Data

Analysis Population Description

Analysis used overall mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 18 values. Table includes only participants with both baseline and post baseline values.

Arm/Group Title	Placebo	Canagliflozin 100 mg	Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.	Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
Measure Participants	226	223	227
Number [Percentage of patients]	11.7	21.6	25.3

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	Odds Ratio (OR)
	Estimated Value	2.55
	Confidence Interval	(2-Sided) 95%; 1.45 to 4.48
	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
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.29
	Confidence Interval	(2-Sided) 95%; 1.88 to 5.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected for the duration of the study, consisting of an 18-week double-blind treatment phase and a 4-week follow-up period.
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 of the treatment arms during the study.
Arm/Group Title	Placebo		Canagliflozin 100 mg		Canagliflozin 300 mg
Arm/Group Description	Each participant received matching placebo once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.		Each participant received 100 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.		Each participant received 300 mg of canagliflozin once daily for 18 weeks with protocol-specified doses of metformin alone or metformin plus sulphonylurea.
All Cause Mortality
	Placebo		Canagliflozin 100 mg		Canagliflozin 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Canagliflozin 100 mg		Canagliflozin 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/226 (1.8%)		5/223 (2.2%)		4/227 (1.8%)
Cardiac disorders
Atrial flutter	0/226 (0%)		0/223 (0%)		1/227 (0.4%)
Infections and infestations
Appendicitis	0/226 (0%)		0/223 (0%)		1/227 (0.4%)
Lung infection	0/226 (0%)		0/223 (0%)		1/227 (0.4%)
Pneumonia	1/226 (0.4%)		0/223 (0%)		1/227 (0.4%)
Tracheitis	0/226 (0%)		1/223 (0.4%)		0/227 (0%)
Injury, poisoning and procedural complications
Spinal compression fracture	0/226 (0%)		1/223 (0.4%)		0/227 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/226 (0%)		0/223 (0%)		1/227 (0.4%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/226 (0%)		1/223 (0.4%)		0/227 (0%)
Rotator cuff syndrome	0/226 (0%)		1/223 (0.4%)		0/227 (0%)
Nervous system disorders
Cerebral infarction	1/226 (0.4%)		0/223 (0%)		0/227 (0%)
Neuritis	1/226 (0.4%)		0/223 (0%)		0/227 (0%)
Neuropathy peripheral	1/226 (0.4%)		0/223 (0%)		0/227 (0%)
Transient ischaemic attack	0/226 (0%)		1/223 (0.4%)		0/227 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	1/226 (0.4%)		0/223 (0%)		0/227 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Canagliflozin 100 mg		Canagliflozin 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/226 (9.7%)		27/223 (12.1%)		27/227 (11.9%)
Infections and infestations
Upper respiratory tract infection	14/226 (6.2%)		7/223 (3.1%)		13/227 (5.7%)
Metabolism and nutrition disorders
Hypoglycaemia	9/226 (4%)		20/223 (9%)		17/227 (7.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.