A Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets in Subjects With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02390050

Recruitment Status : Completed

First Posted : March 17, 2015

Results First Posted : April 20, 2021

Last Update Posted : June 29, 2021

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Sponsor:

Information provided by (Responsible Party):

Theracos

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Diabetes Mellitus, Type 2
Interventions	Drug: Bexagliflozin tablets Drug: Bexagliflozin tablets, placebo
Enrollment	292

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description	Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Period Title: Overall Study
Started	72	72	72	76
Completed	65	67	68	69
Not Completed	7	5	4	7

Baseline Characteristics

Arm/Group Title		Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg	Total
Arm/Group Description		Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...	Total of all reporting groups
Arm/Group Description		Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Total of all reporting groups
Overall Number of Baseline Participants		72	72	72	76	292
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
		58.8 (10.42)	59.0 (10.22)	59.4 (8.99)	59.5 (10.81)	59.2 (10.99)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
	Female	30 41.7%	25 34.7%	31 43.1%	26 34.2%	112 38.4%
	Male	42 58.3%	47 65.3%	41 56.9%	50 65.8%	180 61.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
	Hispanic or Latino	14 19.4%	17 23.6%	12 16.7%	15 19.7%	58 19.9%
	Not Hispanic or Latino	57 79.2%	55 76.4%	58 80.6%	61 80.3%	231 79.1%
	Unknown or Not Reported	1 1.4%	0 0.0%	2 2.8%	0 0.0%	3 1.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
	American Indian or Alaska Native	0 0.0%	1 1.4%	0 0.0%	0 0.0%	1 0.3%
	Asian	37 51.4%	38 52.8%	39 54.2%	41 53.9%	155 53.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	8 11.1%	5 6.9%	9 12.5%	8 10.5%	30 10.3%
	White	27 37.5%	27 37.5%	23 31.9%	26 34.2%	103 35.3%
	More than one race	0 0.0%	1 1.4%	0 0.0%	1 1.3%	2 0.7%
	Unknown or Not Reported	0 0.0%	0 0.0%	1 1.4%	0 0.0%	1 0.3%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
United States		36	36	33	37	142
Japan		36	36	39	39	150
Height Mean (Standard Deviation) Unit of measure: Cm
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
		165.6 (10.63)	165.7 (9.25)	165.8 (9.03)	166.0 (10.33)	165.8 (9.79)
Body Weight Mean (Standard Deviation) Unit of measure: Kg
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
		78.72 (19.747)	80.52 (18.977)	78.39 (17.589)	78.84 (16.740)	79.11 (18.204)
BMI Mean (Standard Deviation) Unit of measure: Kg/m^2
	Number Analyzed	72 participants	72 participants	72 participants	76 participants	292 participants
		28.54 (5.535)	29.10 (5.211)	28.35 (4.978)	28.49 (5.010)	28.62 (5.167)

Outcome Measures

1.Primary Outcome


Title	Change in HbA1c After 12 Weeks of Treatment
Description	Mixed model repeated measures (MMRM) analysis of covariance model (ANC...
Description	Mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA) with baseline HbA1c as a covariate will be fit to the available data, incorporating all visits at which HbA1c was measured for each subject including scheduled visits at Weeks 2, 6, and 12 as well as unscheduled visits for measurements of HbA1c. Treatment (placebo, 5 mg, 10 mg, 20 mg), study center, prior anti-diabetic treatment status, study visit and treatment-by-visit interaction will be applied as fixed effects and subject as a random effect. The least square mean (LSM) change from baseline to Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Subjects who were randomized, took at least one dose of double-blind study medication, and had at least one post-randomization HbA1c measurement were included in the full analysis dataset (FAS). TheHbA1c change from baseline through 12 weeks, and the primary analysis is based on the available data and data obtained after rescue will be excluded and considered missing.


Arm/Group Title	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description:	Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description:	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Number of Participants Analyzed	64	65	68	68
Least Squares Mean (Standard Error) Unit of Measure: percentage of glycated hemoglobin
	0.24 (0.08)	-0.31 (0.08)	-0.44 (0.08)	-0.56 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95% -0.76 to -0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95% -0.89 to -0.47
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95% -1.01 to -0.59
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Proportion of Subjects With HbA1c < 7%
Description	To assess the efficacy of bexagliflozin based on the proportion of sub...
Description	To assess the efficacy of bexagliflozin based on the proportion of subjects who reach the American Diabetes Associate (ADA) and the Japan Diabetes Society target HbA1c of <7%.
Time Frame	Baseline to up to 12 weeks

Outcome Measure Data

Analysis Population Description

Subjects with at least one post-baseline HbA1c value <7% met this endpoint. HbA1c values obtained after start of rescue medication were excluded from this analysis. The number and percentage of subjects with at least one HbA1c value <7% were summarized by treatment group for the FAS.


Arm/Group Title	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description:	Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description:	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Number of Participants Analyzed	72	71	72	75
Measure Type: Count of Participants Unit of Measure: Participants
	11 15.3%	15 21.1%	16 22.2%	27 36.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Odds ratio of having at least 1 post-baseline HbA1c value <7% in the 5 mg bexagliflozin group was compared to placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1308
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Treatment, country, baseline HbA1c and prior anti-diabetic treatment status as predictor variables and a dependable variable of 1 (<7%) or 0 (>7%).

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95% 0.8 to 5.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Odds ratio of having at least 1 post-baseline HbA1c value <7% in the 10 mg bexagliflozin group was compared to placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1294
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Treatment, country, baseline HbA1c and prior anti-diabetic treatment status as predictor variables and a dependable variable of 1 (<7%) or 0 (>7%).

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95% 0.8 to 5.1
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Odds ratio of having at least 1 post-baseline HbA1c value <7% in the 20 mg bexagliflozin group was compared to placebo group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0015
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Treatment, country, baseline HbA1c and prior anti-diabetic treatment status as predictor variables and a dependable variable of 1 (<7%) or 0 (>7%).

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95% 1.7 to 10.3
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Change in Body Weight Over Time
Description	The body weight was analyzed on the full analysis set using the MMRM A...
Description	The body weight was analyzed on the full analysis set using the MMRM ANCOVA model used for the primary efficacy analysis.
Time Frame	Baseline to Week 2, Week 6 and Week 12

Outcome Measure Data

Analysis Population Description

Only subject with a value at the specified time is included


Arm/Group Title		Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description:		Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description:		Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Number of Participants Analyzed		72	71	72	75
Least Squares Mean (Standard Error) Unit of Measure: kg
Week 2	Number Analyzed	71 participants	71 participants	72 participants	75 participants
Week 2		0.00 (0.15)	-0.74 (0.16)	-0.76 (0.15)	-0.99 (0.15)
Week 6	Number Analyzed	70 participants	70 participants	71 participants	75 participants
Week 6		0.02 (0.19)	-1.00 (0.19)	-1.42 (0.19)	-1.49 (0.19)
Week 12	Number Analyzed	69 participants	69 participants	71 participants	69 participants
Week 12		-0.14 (0.25)	-1.58 (0.25)	-1.72 (0.25)	-1.89 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 2: Difference in LS mean change in body weight from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95% -1.13 to -0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 2: Difference in LS mean change in body weight from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95% -1.15 to -0.38
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 2: Difference in LS mean change in body weight from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) 95% -1.38 to -0.61
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 6: Difference in LS mean change in body weight from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95% -1.53 to -0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 6: Difference in LS mean change in body weight from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.45
	Confidence Interval	(2-Sided) 95% -1.95 to -0.94
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 6: Difference in LS mean change in body weight from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.51
	Confidence Interval	(2-Sided) 95% -2.01 to -1.01
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 12: Difference in LS mean change in body weight from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline weight as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.44
	Confidence Interval	(2-Sided) 95% -2.12 to -0.76
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 12: Difference in LS mean change in body weight from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline weight as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.59
	Confidence Interval	(2-Sided) 95% -2.26 to -0.91
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 12: Difference in LS mean change in body weight from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline weight as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.75
	Confidence Interval	(2-Sided) 95% -2.43 to -1.08
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Change in Fasting Plasma Glucose (FPG) Over Time
Description	The fasting plasma glucose (FPG) was analyzed on the full analysis set...
Description	The fasting plasma glucose (FPG) was analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.
Time Frame	Baseline to Week 2, Week 6 and Week 12

Outcome Measure Data

Analysis Population Description

Only subject with a value at the specified time is included


Arm/Group Title		Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description:		Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description:		Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Number of Participants Analyzed		72	71	72	75
Least Squares Mean (Standard Error) Unit of Measure: mmol/L
Week 2	Number Analyzed	71 participants	71 participants	72 participants	75 participants
Week 2		-0.07 (0.16)	-0.55 (0.16)	-0.97 (0.16)	-1.11 (0.15)
Week 6	Number Analyzed	70 participants	70 participants	71 participants	75 participants
Week 6		0.11 (0.17)	-0.82 (0.17)	-1.06 (0.17)	-0.99 (0.17)
Week 12	Number Analyzed	69 participants	69 participants	71 participants	69 participants
Week 12		-0.11 (0.17)	-0.96 (0.17)	-1.16 (0.17)	-1.18 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 2: Difference in LS mean change in FPG from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95% -0.90 to -0.06
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 2: Difference in LS mean change in FPG from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.90
	Confidence Interval	(2-Sided) 95% -1.31 to -0.48
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 2: Difference in LS mean change in FPG from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 95% -1.45 to -0.62
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 6: Difference in LS mean change in FPG from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95% -1.39 to -0.48
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 6: Difference in LS mean change in FPG from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.17
	Confidence Interval	(2-Sided) 95% -1.62 to -0.72
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 6: Difference in LS mean change in FPG from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95% -1.55 to -0.65
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 12: Difference in LS mean change in FPG from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0002
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline FPG as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95% -1.29 to -0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 12: Difference in LS mean change in FPG from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline FPG as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.05
	Confidence Interval	(2-Sided) 95% -1.49 to -0.60
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 12: Difference in LS mean change in FPG from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline FPG as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.07
	Confidence Interval	(2-Sided) 95% -1.52 to -0.63
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Change in Systolic and Diastolic Blood Pressure Over Time
Description	The systolic blood pressure (SBP) and diastolic blood pressure (DBP) w...
Description	The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.
Time Frame	Baseline to Week 2, Week 6 and Week 12

Outcome Measure Data

Analysis Population Description

Only subject with a value at the specified time is included


Arm/Group Title		Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description:		Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description:		Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Number of Participants Analyzed		72	71	72	75
Least Squares Mean (Standard Error) Unit of Measure: mm Hg
Week 2 SBP	Number Analyzed	71 participants	71 participants	72 participants	75 participants
Week 2 SBP		-0.14 (1.42)	-0.33 (1.43)	-2.55 (1.42)	-4.39 (1.38)
Week 2 DBP	Number Analyzed	71 participants	71 participants	72 participants	75 participants
Week 2 DBP		0.15 (0.89)	-0.03 (0.89)	-1.59 (0.88)	-2.00 (0.86)
Week 6 SBP	Number Analyzed	70 participants	70 participants	71 participants	75 participants
Week 6 SBP		-0.57 (1.44)	-1.40 (1.45)	-3.96 (1.44)	-3.07 (1.39)
Week 6 DBP	Number Analyzed	70 participants	70 participants	71 participants	75 participants
Week 6 DBP		-0.52 (0.92)	-0.27 (0.93)	-1.54 (0.92)	-0.36 (0.89)
Week 12 SBP	Number Analyzed	69 participants	69 participants	71 participants	69 participants
Week 12 SBP		1.10 (1.56)	-1.06 (1.57)	-3.30 (1.55)	-2.73 (1.55)
Week 12 DBP	Number Analyzed	69 participants	69 participants	71 participants	69 participants
Week 12 DBP		0.81 (0.95)	-1.43 (0.95)	-0.66 (0.94)	-1.23 (0.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 2: Difference in LS mean change in SBP from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95% -3.90 to 3.51
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 2: Difference in LS mean change in SBP from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.41
	Confidence Interval	(2-Sided) 95% -6.09 to 1.28
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 2: Difference in LS mean change in SBP from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-4.25
	Confidence Interval	(2-Sided) 95% -7.93 to -0.58
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 2: Difference in LS mean change in DBP from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95% -2.50 to 2.13
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 2: Difference in LS mean change in DBP from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.74
	Confidence Interval	(2-Sided) 95% -4.03 to 0.56
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 2: Difference in LS mean change in DBP from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.15
	Confidence Interval	(2-Sided) 95% -4.45 to 0.14
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 6: Difference in LS mean change in SBP from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.84
	Confidence Interval	(2-Sided) 95% -4.57 to 2.90
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 6: Difference in LS mean change in SBP from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-3.39
	Confidence Interval	(2-Sided) 95% -7.12 to 0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 6: Difference in LS mean change in SBP from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.51
	Confidence Interval	(2-Sided) 95% -6.21 to 1.20
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 6: Difference in LS mean change in DBP from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95% -2.15 to 2.66
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 6: Difference in LS mean change in DBP from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95% -3.42 to 1.38
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 6: Difference in LS mean change in DBP from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.84
	Confidence Interval	(2-Sided) 95% -3.22 to 1.54
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 12: Difference in LS mean change in SBP from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.16
	Confidence Interval	(2-Sided) 95% -6.26 to 1.94
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 12: Difference in LS mean change in SBP from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0343
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-4.41
	Confidence Interval	(2-Sided) 95% -8.49 to -0.33
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 12: Difference in LS mean change in SBP from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0679
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-3.83
	Confidence Interval	(2-Sided) 95% -7.95 to 0.28
	Estimation Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 12: Difference in LS mean change in DBP from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0776
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.24
	Confidence Interval	(2-Sided) 95% -4.73 to 0.25
	Estimation Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 12: Difference in LS mean change in DBP from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2415
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-1.47
	Confidence Interval	(2-Sided) 95% -3.95 to 1.00
	Estimation Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 12: Difference in LS mean change in DBP from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1086
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-2.04
	Confidence Interval	(2-Sided) 95% -4.54 to 0.46
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Change in HbA1c Over Time
Description	The least square mean (LSM) change from baseline to Week 2, Week 6 and...
Description	The least square mean (LSM) change from baseline to Week 2, Week 6 and Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes. The LSM change was calculated by excluding HbA1c data obtained after rescue medication.
Time Frame	Baseline to Week 2, Week 6 and Week 12

Outcome Measure Data

Analysis Population Description

Only subject with a value at the specified time is included


Arm/Group Title		Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description:		Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description:		Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Number of Participants Analyzed		72	71	72	75
Least Squares Mean (Standard Error) Unit of Measure: percentage of HbA1c
Week 2	Number Analyzed	69 participants	69 participants	72 participants	74 participants
Week 2		-0.00 (0.04)	-0.09 (0.04)	-0.13 (0.04)	-0.13 (0.04)
Week 6	Number Analyzed	68 participants	66 participants	70 participants	74 participants
Week 6		0.13 (0.06)	-0.32 (0.06)	-0.36 (0.06)	-0.40 (0.06)
Week 12	Number Analyzed	64 participants	65 participants	68 participants	68 participants
Week 12		0.24 (0.08)	-0.31 (0.08)	-0.44 (0.08)	-0.56 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 2: Difference in LS Mean change in HbA1c (%) from baseline to Week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -0.20 to 0.03
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 2: Difference in LS Mean change in HbA1c (%) from baseline to Week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95% -0.24 to -0.02
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 2: Difference in LS Mean change in HbA1c (%) from baseline to Week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95% -0.24 to -0.02
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 6: Difference in LS Mean change in HbA1c (%) from baseline to Week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95% -0.62 to -0.28
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 6: Difference in LS Mean change in HbA1c (%) from baseline to Week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95% -0.66 to -0.32
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 6: Difference in LS Mean change in HbA1c (%) from baseline to Week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95% -0.70 to -0.36
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 5 mg
	Comments	Week 12: Difference in LS Mean change in HbA1c (%) from baseline to Week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95% -0.76 to -0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 10 mg
	Comments	Week 12: Difference in LS Mean change in HbA1c (%) from baseline to Week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95% -0.89 to -0.47
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Bexagliflozin 20 mg
	Comments	Week 12: Difference in LS Mean change in HbA1c (%) from baseline to Week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	P-value from Type III F-test
	Method	ANCOVA
	Comments	Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates

Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95% -1.01 to -0.59
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
Arm/Group Description	Placebo tablet once daily before br...	Bexagliflozin tablet, 5 mg, once da...	Bexagliflozin tablet, 10 mg, once d...	Bexagliflozin tablet, 20 mg, once d...
Arm/Group Description	Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
All-Cause Mortality
	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	0/76 (0.00%)
Serious Adverse Events Serious Adverse Events
	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/72 (0.00%)	0/72 (0.00%)	3/72 (4.17%)	2/76 (2.63%)
Cardiac disorders
Acute myocardial infarction ^† 1	0/72 (0.00%)	0/72 (0.00%)	1/72 (1.39%)	0/76 (0.00%)
Hepatobiliary disorders
Bile duct stone ^† 1	0/72 (0.00%)	0/72 (0.00%)	1/72 (1.39%)	0/76 (0.00%)
Infections and infestations
Urinary Tract Infection ^† 1	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	1/76 (1.32%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant ^† 1	0/72 (0.00%)	0/72 (0.00%)	1/72 (1.39%)	0/76 (0.00%)
Gastroesophageal cancer ^† 1	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	1/76 (1.32%)
1 Term from vocabulary, MedDRA 17.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Placebo	Bexagliflozin 5 mg	Bexagliflozin 10 mg	Bexagliflozin 20 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	12/72 (16.67%)	15/72 (20.83%)	18/72 (25.00%)	17/76 (22.37%)
Eye disorders
Vision blurred ^† 1	0/72 (0.00%)	2/72 (2.78%)	0/72 (0.00%)	0/76 (0.00%)
Gastrointestinal disorders
Nausea ^† 1	2/72 (2.78%)	0/72 (0.00%)	0/72 (0.00%)	0/76 (0.00%)
Diarrhea ^† 1	2/72 (2.78%)	2/72 (2.78%)	1/72 (1.39%)	0/76 (0.00%)
General disorders
Thirst ^† 1	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	2/76 (2.63%)
Infections and infestations
Nasopharyngitis ^† 1	3/72 (4.17%)	5/72 (6.94%)	4/72 (5.56%)	3/76 (3.95%)
Pharyngitis ^† 1	0/72 (0.00%)	2/72 (2.78%)	3/72 (4.17%)	0/76 (0.00%)
Urinary tract infection ^† 1	1/72 (1.39%)	2/72 (2.78%)	1/72 (1.39%)	1/76 (1.32%)
Viral upper respiratory tract infection ^† 1	0/72 (0.00%)	0/72 (0.00%)	2/72 (2.78%)	0/76 (0.00%)
Upper respiratory tract infection ^† 1	2/72 (2.78%)	0/72 (0.00%)	1/72 (1.39%)	0/76 (0.00%)
Metabolism and nutrition disorders
Hypoglycemia ^† 1	1/72 (1.39%)	0/72 (0.00%)	0/72 (0.00%)	4/76 (5.26%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/72 (1.39%)	0/72 (0.00%)	2/72 (2.78%)	0/76 (0.00%)
Muscle spasms ^† 1	2/72 (2.78%)	1/72 (1.39%)	0/72 (0.00%)	1/76 (1.32%)
Arthralgia ^† 1	0/72 (0.00%)	1/72 (1.39%)	2/72 (2.78%)	1/76 (1.32%)
Nervous system disorders
Dizziness ^† 1	1/72 (1.39%)	2/72 (2.78%)	0/72 (0.00%)	0/76 (0.00%)
Headache ^† 1	2/72 (2.78%)	2/72 (2.78%)	2/72 (2.78%)	2/76 (2.63%)
Renal and urinary disorders
Dysuria ^† 1	1/72 (1.39%)	0/72 (0.00%)	0/72 (0.00%)	3/76 (3.95%)
Polyuria ^† 1	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	3/76 (3.95%)
Pollakiuria ^† 1	0/72 (0.00%)	2/72 (2.78%)	2/72 (2.78%)	2/76 (2.63%)
Reproductive system and breast disorders
Balanoposthitis ^† 1	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	2/76 (2.63%)
Skin and subcutaneous tissue disorders
Dermatitis ^† 1	0/72 (0.00%)	0/72 (0.00%)	0/72 (0.00%)	2/76 (2.63%)
1 Term from vocabulary, MedDRA 17.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Investigator has no publication right.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Albert Collinson
Organization:	Theracos Sub, LLC
Phone:	(508) 630-2129
EMail:	acollinson@theracos.com

Publications:

American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.

Look AHEAD Research Group; Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24. Erratum In: N Engl J Med. 2014 May 8;370(19):1866.

Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A; Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009 Jun;53(6):982-92. doi: 10.1053/j.ajkd.2008.12.034. Epub 2009 Apr 1.

National Research Council (US) Panel on Handling Missing Data in Clinical Trials. The Prevention and Treatment of Missing Data in Clinical Trials. Washington (DC): National Academies Press (US); 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK209904/

Palaniappan LP, Wong EC, Shin JJ, Fortmann SP, Lauderdale DS. Asian Americans have greater prevalence of metabolic syndrome despite lower body mass index. Int J Obes (Lond). 2011 Mar;35(3):393-400. doi: 10.1038/ijo.2010.152. Epub 2010 Aug 3.

Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, Li Volti S, Neuhaus T, Skovby F, Swift PG, Schaub J, Klaerke D. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol. 2003 Nov;14(11):2873-82. doi: 10.1097/01.asn.0000092790.89332.d2.

Scheen AJ, Van Gaal LF. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes. Lancet Diabetes Endocrinol. 2014 Nov;2(11):911-22. doi: 10.1016/S2213-8587(14)70004-X. Epub 2014 Feb 19.

Schwartz S, Fabricatore AN, Diamond A. Weight reduction in diabetes. Adv Exp Med Biol. 2012;771:438-58. doi: 10.1007/978-1-4614-5441-0_31.

van den Heuvel LP, Assink K, Willemsen M, Monnens L. Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum Genet. 2002 Dec;111(6):544-7. doi: 10.1007/s00439-002-0820-5. Epub 2002 Sep 27.

Japan Diabetes Society (2012). Treatment Guidance for Diabetes 2012-2013.

Layout table for additonal information

Responsible Party:	Theracos
ClinicalTrials.gov Identifier:	NCT02390050
Other Study ID Numbers:	THR-1442-C-449
First Submitted:	March 11, 2015
First Posted:	March 17, 2015
Results First Submitted:	March 25, 2021
Results First Posted:	April 20, 2021
Last Update Posted:	June 29, 2021

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