Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment

• Sponsor: Theracos (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02836873
• Collaborator: (none)
• Enrollment: 312
• Locations: 56
• Arms: 2
• Actual Duration (Months): 15.6
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This was a phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of oral administration of bexagliflozin at 20 mg versus placebo in subjects with T2DM, moderate renal impairment and inadequate glycemic control.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Bexagliflozin; Drug: Placebo	Phase 3

Detailed Description

The phase 3, double-blind, placebo-controlled parallel-group study was conducted at investigative sites in the US, Japan, France and Spain. Approximately 300 subjects were to be randomly assigned to receive bexagliflozin tablets, 20 mg, or placebo in equal ratio for 24 weeks.

The study was to enrolled male and female participants who had T2DM with an HbA1c between 7.0 and 10.5% (inclusive) and stage 3 chronic kidney disease (CKD) as defined by an eGFR of ≥ 30 and< 60 mL min-1 per 1.73 m2 at the screening visit and one additional time of measurement between 1 and 12 months prior to screening. Subjects were either treatment naïve or were treated with a stable regimen of anti-diabetic medications.

All eligible subjects were to enter a one-week single-blind, placebo run-in period. Subjects who were compliant in taking run-in medication, had screening eGFR ≥ 30 and< 60 mL min-1 per 1.73 m2, and had stable GFR (no more than 20% change in eGFR between a historical value and the value determined at the screening visit) were eligible for randomization. Randomization was stratified by HbA1c level (7.0 to 8.5% or 8.6 to 10.5%), anti-diabetic treatment regimen and eGFR (30 - 44 mL min-1 per 1.73 m2 or 45 - 59 mL min-1 per 1.73 m2). At least 135 subjects in each of the eGFR groups were planned.

Study subjects were to schedule clinic visits at weeks 2, 6, 12, 18, and 24 for safety and efficacy evaluation. At weeks 2 and 18, the visits were to be conducted via phone interviews unless an in-person visit was considered clinically advisable. A final follow-up visit was to be conducted at week 26 or two weeks after the last dose of investigational product if the subject withdrew prior to week 24.

Study Design

• Study Type: Interventional
• Actual Enrollment: 312 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double Blind Placebo Controlled Study to Evaluate the Effect of Bexagliflozin Tablets on Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus and Moderate Renal Impairment
• Actual Study Start Date: Sep 23, 2016
• Actual Primary Completion Date: Jan 11, 2018
• Actual Study Completion Date: Jan 11, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bexagliflozin tablets, 20 mg Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Drug: Bexagliflozin; Bexagliflozin tablet, 20 mg; Other Names: EGT0001442 EGT0001474
Placebo Comparator: Placebo tablets Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.	Drug: Placebo; Placebo (inactive) tablet to match the active comparator

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c at 24 Weeks [24 weeks]

   The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with moderate renal impairment.

Secondary Outcome Measures

1. Change in Body Weight From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 [24 weeks]

   A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in BMI from baseline to week 24 in subjects with a BMI ≥ 25 kg/m2.

2. Change From Baseline in Systolic Blood Pressure (SBP) in Subjects With Baseline SBP ≥ 130 mm Hg at Week 24 [24 weeks]

   A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change from baseline in SBP to in subjects with baseline SBP ≥ 130 mm Hg at Week 24.

3. Change From Baseline in HbA1c in Subjects With Stage 3a CKD (eGFR 45 to 59 mL/Min/1.73 m2) at Week 24 [24 weeks]

   A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3a CKD (eGFR 45 to 59 mL/min/1.73 m2) at week 24.

4. Change From Baseline in HbA1c in Subjects With Stage 3b CKD (eGFR 30 to 44 mL/Min/1.73 m2) at Week 24 [24 weeks]

   A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3b CKD (eGFR 30 to 44 mL/min/1.73 m2) at week 24.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Each subject was required to meet the following criteria at the time of enrollment to be eligible for the study:

1. To have been male or non-pregnant female ≥ 20 years of age. Women of childbearing potential were required to agree to use contraception throughout the study to avoid any possible pregnancy. Females who were surgically sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses for greater than 12 months and age

45 years) were eligible if they tested negative on the urine pregnancy test.

1. To have had a diagnosis of T2DM with an HbA1c between 7.0 and 10.5% (inclusive) at the time of screening.

2. To have been treatment naïve or to have been treated with a stable regimen of anti-diabetic medications. At the time of screening, the doses and frequency of all anti-diabetic medications were to have been stable for 8 weeks.

3. To have had an eGFR ≥ 30 and < 60 mL min-1 per 1.73 m2 at 2 time points: screening (V1), and 1 additional time point between 1 and 12 months of screening (may be obtained from available medical records). The eGFR was calculated by the MDRD equation.

4. To have had a body mass index (BMI) ≤ 45 kg per m2 (inclusive).

5. To have been taking stable doses of medications for hypertension or hyperlipidemia (if applicable) for at least 30 days prior to randomization

6. To have had stable eGFR between the historic value and day of screening (no more than 20% change in eGFR between the most recent historical value and the value determined at the screening visit V1).

9.3.2 Exclusion Criteria

Potential participants who exhibited any of the following characteristics were excluded from the study:

1. A diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY)

2. A hemoglobinopathy that could affect HbA1c measurement

3. Frequent symptomatic hypoglycemia (greater than one episode per week on average)

4. A history of genitourinary tract infection within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within the last 6 months

5. A cancer, active or in remission for < 3 years (Non-melanoma skin cancer or basal cell carcinoma or carcinoma in situ of the cervix were not grounds for exclusion)

6. A history of alcohol or illicit drug abuse in the past 2 years

7. Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase > 1.5 × upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN

8. A history of MI, stroke or hospitalization for heart failure, or hospitalization for unstable angina in the prior 3 months

9. Evidence of NYHA class IV heart failure at screening or randomization

10. A history of taking an SGLT2 inhibitor within 3 months of screening

11. Any condition, disease, disorder, or clinically relevant laboratory abnormality that, in the opinion of the PI, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment

12. A current status of pregnancy or breastfeeding

13. A current status of renal replacement therapy (peritoneal or hemodialysis) or a history of renal transplantation

14. A corrected serum calcium < 8 mg dL-1 at screening (V1) or randomization (V3)

15. Uncontrolled hypertension (systolic blood pressure >170 mm Hg or diastolic blood pressure >110 mm Hg)

16. Participation in another interventional trial or exposure to an investigational drug within 30 days or 7 half-lives of screening, whichever was longer

17. Previous exposure to bexagliflozin or EGT0001474

18. Evidence of having skipped dosing more than once during the run-in period

19. A fasting blood glucose value during the run-in period ≥ 250 mg dL-1 (13.9 mmol L-1) associated with severe clinical signs or symptoms of hyperglycemia

20. Any episode of symptomatic hypoglycemia during the run-in period in which symptoms were severe

21. An inability to comprehend or unwillingness to provide written informed consent in accordance with institutional and regulatory guidelines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fresno	California	United States	93720
2	Research Site	La Palma	California	United States	90623
3	Research Site	Lincoln	California	United States	95648
4	Research Site	Riverside	California	United States	92505
5	Research Site	Sacramento	California	United States	95825
6	Research Site	San Dimas	California	United States	91773
7	Research Site	Monument	Colorado	United States	80132
8	Research Site	Norwalk	Connecticut	United States	06851
9	Research Site	Hollywood	Florida	United States	33024
10	Research Site	Tampa	Florida	United States	33607
11	Research Site	West Palm Beach	Florida	United States	33401
12	Research Site	Paducah	Kentucky	United States	42003
13	Research Site	Auburn	Maine	United States	04210
14	Research Site	Rockport	Maine	United States	04856
15	Research Site	Nashua	New Hampshire	United States	03063
16	Research Site	Bronx	New York	United States	10461
17	Research Site	Stow	Ohio	United States	44224
18	Research Site	Oklahoma City	Oklahoma	United States	73112
19	Research Site	Austin	Texas	United States	78731
20	Research Site	Austin	Texas	United States	78758
21	Research Site	North Richland Hills	Texas	United States	76180
22	Research Site	Round Rock	Texas	United States	78681
23	Research Site	San Antonio	Texas	United States	78229
24	Research Site	Dijon		France	21079
25	Research Site	Paris		France	75010
26	Research Site	Paris		France	75013
27	Research Site	Paris		France	75877
28	Research Site	Pierre Benite		France	69310
29	Research Site	Poitiers		France	86021
30	Research Site	Venissieux		France	69200
31	Research Site	Atsugi-shi	Kanagawa	Japan	243-0035
32	Research Site	Kamakura-shi	Kanagawa	Japan	247-0056
33	Research Site	Kawasaki-shi	Kanagawa	Japan	210-0852
34	Research Site	Yokohama-shi	Kanagawa	Japan	221-0802
35	Research Site	Yokohama-shi	Kanagawa	Japan	231-0023
36	Research Site	Yokohama-shi	Kanagawa	Japan	241-0821
37	Research Site	Kyoto-shi	Kyoto	Japan	600-8898
38	Research Site	Kyoto-shi	Kyoto	Japan	615-8125
39	Research Site	Kawagoe-shi	Saitama	Japan	350-0851
40	Research Site	Kawaguchi-shi	Saitama	Japan	332-0021
41	Research site	Sayama-shi	SAitama	Japan	350-1305
42	Research Site	Hachioji-shi	Tokyo	Japan	192-0918
43	Research Site	Hachioji-shi	Tokyo	Japan	193-0811
44	Research Site	Minato-ku	Tokyo	Japan	108-0075
45	Research Site	Ota-ku	Tokyo	Japan	143-0015
46	Research Site	Shinagawa-ku	Tokyo	Japan	141-0032
47	Research Site	Toshima-ku	Toyko	Japan	171-0021
48	Research Site	Alcala de Henares		Spain	28805
49	Research Site	Alicante		Spain	03004
50	Research Site	Madrid		Spain	28006
51	Research Site	Madrid		Spain	28009
52	Research Site	Malaga		Spain	29009
53	Research Site	Malaga		Spain	29010
54	Research Site	Sevilla		Spain	41009
55	Research Site	Valencia		Spain	46026
56	Research Site	Valencia		Spain	46600

Sponsors and Collaborators

• Theracos

Investigators

• Study Director: Andrew Allegretti, M.D., Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol - Oct 25, 2016
• Statistical Analysis Plan - Dec 8, 2017

More Information

Publications

None provided.

• Responsible Party: Theracos
• ClinicalTrials.gov Identifier: NCT02836873
• Other Study ID Numbers: THR-1442-C-448
• First Posted: Jul 19, 2016
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Bexagliflozin

Study Results

Participant Flow

Arm/Group Title	Bexagliflozin 20 mg	Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Period Title: Overall Study
STARTED	157	155
COMPLETED	152	144
NOT COMPLETED	5	11

Baseline Characteristics

Arm/Group Title	Bexagliflozin 20 mg	Placebo	Total
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.	Total of all reporting groups
Overall Participants	157	155	312
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.3 (8.36)	69.9 (8.29)	69.6 (8.32)
Sex: Female, Male (Count of Participants)
Female	65 41.4%	51 32.9%	116 37.2%
Male	92 58.6%	104 67.1%	196 62.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 4.5%	17 11%	24 7.7%
Not Hispanic or Latino	149 94.9%	138 89%	287 92%
Unknown or Not Reported	1 0.6%	0 0%	1 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	61 38.9%	59 38.1%	120 38.5%
Native Hawaiian or Other Pacific Islander	2 1.3%	0 0%	2 0.6%
Black or African American	9 5.7%	6 3.9%	15 4.8%
White	83 52.9%	88 56.8%	171 54.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.3%	2 1.3%	4 1.3%
Region of Enrollment (participants) [Number]
United States	53 33.8%	50 32.3%	103 33%
Japan	58 36.9%	58 37.4%	116 37.2%
France	12 7.6%	16 10.3%	28 9%
Spain	34 21.7%	31 20%	65 20.8%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	164.8 (9.94)	164.7 (10.58)	164.8 (10.25)
Body Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82.90 (20.509)	82.59 (21.196)	82.75 (20.820)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.29 (5.988)	30.10 (5.774)	30.20 (5.874)
SBP Categories (Count of Participants)
< 130 mm Hg	50 31.8%	42 27.1%	92 29.5%
> 130 mm Hg	107 68.2%	113 72.9%	220 70.5%
eGFR in Sub-group (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
Stage 3a CKD: eGFR High Group	51.76 (5.307)	51.27 (4.404)	51.52 (4.884)
Stage 3b CKD: eGFR Low Group	37.79 (4.572)	37.87 (4.629)	37.83 (4.586)
Subjects in eGFR Sub-group at Baseline (Count of Participants)
Stage 3a CKD: eGFR High Group	86 54.8%	80 51.6%	166 53.2%
Stage 3b CKD: eGFR Low Group	71 45.2%	75 48.4%	146 46.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c at 24 Weeks
Description	The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with moderate renal impairment.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bexagliflozin 20 mg	Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Measure Participants	157	155
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.59 (0.065)	-0.31 (0.066)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin 20 mg, Placebo
	Comments	This is a mixed-effects repeated measures analysis including region, screening anti-diabetic treatment regimen, baseline eGFR, treatment, visit, treatment-by-visit interaction and baseline HbA1c as a fixed effect covariate. Data from Weeks 6, 12, and 24 are used in the model.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	Mixed-effects repeated measures
	Comments	Region, screening anti-diabetic treatment, baseline eGFR, treatment, visit, treatment-by-visit and baseline HbA1c value as fixed effect covariates.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.46 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Body Weight From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2
Description	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in BMI from baseline to week 24 in subjects with a BMI ≥ 25 kg/m2.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Only number of subjects with a value at baseline and at the specific visit is included.

Arm/Group Title	Bexagliflozin 20 mg	Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Measure Participants	122	117
Least Squares Mean (Standard Error) [kg]	-2.31 (0.265)	-0.55 (0.269)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed-effects repeated measures
	Comments	Region, screening anti-diabetic treatment, baseline eGFR, treatment, visit, treatment-by-visit and baseline HbA1c value as fixed effect covariates.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.76
	Confidence Interval	(2-Sided) 95%; -2.50 to -1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) in Subjects With Baseline SBP ≥ 130 mm Hg at Week 24
Description	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change from baseline in SBP to in subjects with baseline SBP ≥ 130 mm Hg at Week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Only number of subjects with a value at baseline and at Week 24 is included.

Arm/Group Title	Bexagliflozin 20 mg	Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Measure Participants	104	108
Least Squares Mean (Standard Error) [mm Hg]	-10.14 (1.477)	-7.51 (1.460)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2035
	Comments
	Method	Mixed-effects repeated measures
	Comments	Region, screening anti-diabetic treatment, baseline eGFR, treatment, visit, treatment-by-visit and baseline HbA1c value as fixed effect covariates.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.63
	Confidence Interval	(2-Sided) 95%; -6.70 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in HbA1c in Subjects With Stage 3a CKD (eGFR 45 to 59 mL/Min/1.73 m2) at Week 24
Description	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3a CKD (eGFR 45 to 59 mL/min/1.73 m2) at week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Subjects who had the eGFR between 45 and 59 mL/min/1.73 m2 are included in this analysis.

Arm/Group Title	Bexagliflozin 20 mg	Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Measure Participants	86	80
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.63 (0.086)	-0.44 (0.089)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1156
	Comments
	Method	Mixed-effects repeated measures
	Comments	Region, screening anti-diabetic treatment, baseline eGFR, treatment, visit, treatment-by-visit and baseline HbA1c value as fixed effect covariates.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in HbA1c in Subjects With Stage 3b CKD (eGFR 30 to 44 mL/Min/1.73 m2) at Week 24
Description	A secondary objective is to evaluate the effect of bexagliflozin 20 mg on the placebo-adjusted change in HbA1c from baseline in subjects with stage 3b CKD (eGFR 30 to 44 mL/min/1.73 m2) at week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Subjects with eGFR between 30 and 44 mL/min/1.73 m2 were included in this anlaysis.

Arm/Group Title	Bexagliflozin 20 mg	Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.	Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
Measure Participants	71	75
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.57 (0.100)	-0.20 (0.097)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments
	Method	Mixed-effects repeated measures
	Comments	Region, screening anti-diabetic treatment, baseline eGFR, treatment, visit, treatment-by-visit and baseline HbA1c value as fixed effect covariates.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data was collected from Week -1 (Visit 2) to Week 26 (Visit 29).
Arm/Group Title	Bexagliflozin 20 mg		Placebo
Arm/Group Description	Each subject will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study.		Each subject will receive a placebo (inactive) tablet once daily for the duration of the study.
All Cause Mortality
	Bexagliflozin 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/157 (0%)		0/155 (0%)
Serious Adverse Events
	Bexagliflozin 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/157 (7%)		9/155 (5.8%)
Cardiac disorders
Bundle branch block left	1/157 (0.6%)		0/155 (0%)
Cardiogenic shock	0/157 (0%)		1/155 (0.6%)
Coronary artery disease	0/157 (0%)		1/155 (0.6%)
Myocardial infarction	1/157 (0.6%)		0/155 (0%)
Ear and labyrinth disorders
Deafness unilateral	1/157 (0.6%)		0/155 (0%)
Gastrointestinal disorders
Gastritis erosive	1/157 (0.6%)		0/155 (0%)
Intestinal ischemia	0/157 (0%)		1/155 (0.6%)
Esophagitis	1/157 (0.6%)		0/155 (0%)
Pancreatitis acute	0/157 (0%)		1/155 (0.6%)
Hepatobiliary disorders
Cholecystitis acute	0/157 (0%)		1/155 (0.6%)
Infections and infestations
Gastroenteritis	0/157 (0%)		1/155 (0.6%)
Lower respiratory tract infection	0/157 (0%)		1/155 (0.6%)
Sepsis	1/157 (0.6%)		0/155 (0%)
Metabolism and nutrition disorders
Hypoglycemia	1/157 (0.6%)		0/155 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/157 (0.6%)		0/155 (0%)
Lumbar spinal stenosis	1/157 (0.6%)		0/155 (0%)
Neuropathic anthropathy	0/157 (0%)		1/155 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma colon	1/157 (0.6%)		0/155 (0%)
Colon cancer	0/157 (0%)		1/155 (0.6%)
Gastric cancer	0/157 (0%)		1/155 (0.6%)
Rectal adenocarcinoma	0/157 (0%)		1/155 (0.6%)
Nervous system disorders
Carotid artery disease	1/157 (0.6%)		0/155 (0%)
Cerebral infarction	1/157 (0.6%)		0/155 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea exertional	1/157 (0.6%)		0/155 (0%)
Respiratory distress	0/157 (0%)		1/155 (0.6%)
Vascular disorders
Orthostatic hypotension	0/157 (0%)		1/155 (0.6%)
Other (Not Including Serious) Adverse Events
	Bexagliflozin 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/157 (35.7%)		42/155 (27.1%)
Gastrointestinal disorders
Nausea	8/157 (5.1%)	9	11/155 (7.1%)	12
Infections and infestations
Nasopharyngitis	11/157 (7%)	13	13/155 (8.4%)	21
Urinary tract infection	10/157 (6.4%)	12	5/155 (3.2%)	5
Bronchitis	8/157 (5.1%)	8	2/155 (1.3%)	2
Metabolism and nutrition disorders
Hypoglycaemia	40/157 (25.5%)	258	40/155 (25.8%)	261
Musculoskeletal and connective tissue disorders
Arthralgia	9/157 (5.7%)	11	5/155 (3.2%)	5
Renal and urinary disorders
Polyuria	12/157 (7.6%)	15	7/155 (4.5%)	7
Acute kidney injury	8/157 (5.1%)	9	6/155 (3.9%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The PI has no right to publish the trial results.