Safety and Efficacy of Bexagliflozin Compared to Placebo... | NCT03259789

Status Module

Description Module

Label	Type	Intervention Names
Bexagliflozin tablets, 20 mg; Double-Blind	Active Comparator	Drug: Bexagliflozin tablets, 20 mg
Bexagliflozin tablets, Placebo; Double Blind	Placebo Comparator	Drug: Bexagliflozin tablets, placebo
Bexagliflozin Tablets, 20 mg; High Glycemic Group	Experimental	Drug: Bexagliflozin tablets, 20 mg

Name	Type	Description	Arm Group Labels	Other Names
Bexagliflozin tablets, 20 mg	Drug	Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.	Bexagliflozin tablets, 20 mg; Double-Blind

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c at Week 24 for Double-blind Group	HbA1c was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.	Baseline to week 24
Change From Baseline in HbA1c at Week 24 for High Glycemic Group	The change in HbA1c from baseline at Week 24 in High Glycemic Group was calculated by subtracting the mean HbA1c at baseline from the mean HbA1c at Week 24	Baseline to week 24

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for Double-blind Group	FPG was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.	Baseline, up to 24 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for High Glycemic Group

Eligibility Module

Eligibility Criteria

The subjects were required to meet the following criteria at the time of enrollment to be eligible for the study:

Had been age ≥ 20 years at screening. Women of childbearing potential were required to have tested negative for pregnancy and have agreed to abstinence or contraception for the duration of the study to avoid any possible pregnancy. Females who were surgically sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses greater than 12 months) were eligible if they had tested negative for pregnancy at screening.
a) Had a history of T2DM with an HbA1c level of ≥ 7.5% and ≤ 10.5% at screening, or b) Had a history of T2DM with an HbA1c level of >10.5% and ≤ 12.0% at screening
Had been prescribed a stable dose of metformin (≥1500 mg per day in the US or ≥ 1000 mg per day in Japan) as their sole anti-diabetic medication
Had a body mass index (BMI) ≤ 45 kg m-2
Had been able to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines
Had no recent changes to their medications for hypertension or hyperlipidemia (if applicable)
Had the ability to regularly self-administer medication, as evidenced by consumption of all, or at worst one less than all, doses of run-in medication prior to randomization

Subjects who met any of the following criteria were to be excluded from the study:

Had a diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young
Were pregnant or breastfeeding
Had one or more hemoglobin alleles that affect HbA1c measurement
Had a history of genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis) within 6 weeks of screening or a history of ≥ 3 genitourinary infections requiring treatment within 6 months of screening
Had an estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL min-1 per 1.73 m2
Had a sitting systolic blood pressure >180 mmHg or a sitting diastolic blood pressure > 110 mmHg at screening
Had exposure to hypoglycemic agent(s) other than metformin during the 8 weeks prior to screening
Had a history of illicit drug use or alcohol abuse in the past 2 years
Had a life expectancy < 2 years
Had a diagnosis of New York Heart Association (NYHA) Class IV heart failure within 3 months of screening
Had experienced an MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening
Had exposure to an investigational drug within 30 days
Had a previous exposure to bexagliflozin or EGT0001474
Had a history of SGLT2 inhibitor treatment
Were participating in another interventional trial
Were not able to comply with the study scheduled visits
Had any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the primary investigator, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment
Had an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 × ULN or total bilirubin ≥ 1.5 × ULN at screening

Name	Affiliation	Role
J, Paul Lock, M.D.	Theracos	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Site 1232		Birmingham	Alabama	35205	United States
Clinical Research Site 1378

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
FG001	Double-blind Group: Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 26, 2017	Mar 28, 2020

Arm/Group Information

ID	Title	Description
BG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
BG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
BG002	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Total number of participants for Double-blind group is 317. The number of participants for High Glycemic group is 34.

For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.

Mean

Standard Deviation

years

Title	Denominators	Categories
Double-blind Group	ParticipantsBG000158 ParticipantsBG001159 ParticipantsBG0020 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000158 ParticipantsBG001159 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000158 ParticipantsBG001159 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000158 ParticipantsBG001159 ParticipantsBG002

Region of Enrollment

Number

participants

Title	Denominators	Categories
United States	ParticipantsBG000158 ParticipantsBG001159 ParticipantsBG002

Height

Total number of participants for Double-blind group is 317. The number of subjects for High Glycemic group is 34.

Mean

Standard Deviation

Title	Denominators	Categories
Double-blind Group	ParticipantsBG000158 ParticipantsBG001159

Body Weight

Total number of participants for Double-blind group is 317. The number of participants for High Glycemic group is 34.

Mean

Standard Deviation

Title	Denominators	Categories
Double-blind Group	ParticipantsBG000158 ParticipantsBG001159

BMI

Total number of participants for Double-blind group is 317. The number of participants for High Glycemic group is 34.

Mean

Standard Deviation

kg/m^2

Title	Denominators	Categories
Double-blind Group	ParticipantsBG000158 ParticipantsBG001159

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in HbA1c at Week 24 for Double-blind Group

HbA1c was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.

The intention-to-treat (ITT) population was used for the primary analysis. Subjects with a value at baseline and at week 24 were analyzed.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline to week 24

ID	Title	Description
OG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000142 OG001145

Title

Denominators

Categories

Title	Measurements
	OG000-1.09± 0.076 OG001-0.56± 0.075

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed-effects repeated measures	Mixed-effects repeated measures analysis includes country, treatment, visit, treatment and baseline HbA1c value as fixed effect covariates	< 0.0001		Difference of LS Means	-0.53			2-Sided	95	-0.74	-0.32					Superiority

Primary

Change From Baseline in HbA1c at Week 24 for High Glycemic Group

The change in HbA1c from baseline at Week 24 in High Glycemic Group was calculated by subtracting the mean HbA1c at baseline from the mean HbA1c at Week 24

The intention-to-treat (ITT) population was used for the primary analysis. Subjects with a value at baseline and at week 24 were analyzed.

Posted

Mean

Standard Deviation

percentage of HbA1c

Baseline to week 24

ID	Title	Description
OG000	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for Double-blind Group

FPG was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.

ITT population was used for the analysis. Subjects with a value at baseline and at week 24 were analyzed.

Posted

Least Squares Mean

Standard Error

mmol/L

Baseline, up to 24 weeks

ID	Title	Description
OG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for High Glycemic Group

The change in FPG from baseline at Week 24 for High Glycemic Group was calculated by subtracting the mean FPG at baseline from the mean FPG at Week 24

ITT population was used for the analysis. Subjects with a value at baseline and at week 24 were analyzed.

Posted

Mean

Standard Deviation

mmol/L

Baseline, up to 24 weeks

ID	Title	Description
OG000	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Systolic Blood Pressure (SBP) at Week 24

Changes from baseline at Week 24 in SBP for the double-blind group and high glycemic group

The ITT population was used for the analysis. Subjects with a value at baseline and at the specific visit were analyzed.

Posted

Least Squares Mean

Standard Error

mm Hg

Baseline to week 24

ID	Title	Description
OG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG002	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Secondary

Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group

The proportion of subjects who achieved HbA1c < 7% at 6, 12, 18 and 24 weeks were calculated based on the number of subjects with a value at each time point for each group. The model-adjusted proportion was calculated based on a logistic analysis using Generalized Estimating Equation (GEE) logistic regression that includes country, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate. An unstructured correlation structure will be used, or autoregressive if the model with the unstructured structure does not converge.

The number of subjects in the ITT population with a value at baseline and at the specified visit was included. Model-adjusted proportion (LS proportion) and 95% confidence interval were reported for Double-blind Treatment Group.

Posted

Least Squares Mean

95% Confidence Interval

Proportion of subjects

Baseline, up to 24 weeks

ID	Title	Description
OG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Secondary

Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group

The proportion of subjects who achieved HbA1c < 7% at 6, 12, 18 and 24 weeks were calculated based on the number of subjects with a value at each time point for each group.

The number of subjects in the ITT population with a value at baseline and at the specified visit was included. Proportion of subjects achieving HbA1c < 7% was reported for High Glycemic Group without a 95% confidence interval.

Posted

Number

Proportion of subjects

Baseline, up to 24 weeks

ID	Title	Description
OG000	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000

Secondary

Change in Body Mass From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 for Double-blind Group

Changes in body mass from baseline to week 24 was calculated based on LS means for both bexagliflozin and placebo groups.

Subjects with a BMI >= 25 kg/m2 at baseline in the ITT population were included. The number of subjects with a value at baseline and at week 24 was analyzed. Model-adjusted mean change (LS Mean) and standard error (SE) were reported.

Posted

Least Squares Mean

Standard Error

Baseline to week 24

ID	Title	Description
OG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants

Secondary

Change in Body Mass From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 for High Glycemic Group

The change in body mass from baseline at week 24 for High Glycemic group was calculated by subtracting the mean body mass at baseline from the mean body mass at week 24

Subjects with a BMI >= 25 kg/m2 at baseline in the ITT population were included. The number of subjects with a value at baseline and at week 24 was analyzed.

Posted

Mean

Standard Deviation

Baseline to week 24

ID	Title	Description
OG000	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in HbA1c Over Time in Double-blind Treatment Group

The change from baseline in HbA1c at 6, 12, 18 and 24 weeks was calculated based on the number of subjects with a value at each time point for each group. The model-adjusted change from baseline was calculated based on a mixed-effects repeated measures analysis that includes country, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.

The Number Analyzed only includes the number of subjects with a value at baseline and at the specific visit. Model-adjusted mean change (LS Mean) and standard error (SE) were reported for Double-blind Treatment Group.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, up to 24 weeks

ID	Title	Description
OG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
OG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Secondary

Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and ≤ 12.0%

The change from baseline in HbA1c at 6, 12, 18 and 24 weeks was calculated based on the number of subjects with a value at each time point in High Glycemic Group.

The Number Analyzed only includes the number of subjects with a value at baseline and at the specific visit.

Posted

Mean

Standard Deviation

percentage of HbA1c

Baseline, up to 24 weeks

ID	Title	Description
OG000	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-blind Group: Bexagliflozin 20 mg	Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	158	3	158	16	158
EG001	Double-blind Group: Placebo	Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	159	4	159	28	159
EG002	High Glycemic Group	Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	34	0	34	7	34

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected158 at risk EG0010 events0 affected159 at risk EG0020 events0 affected34 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected158 at risk EG0011 events1 affected159 at risk EG0020 events0 affected34 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected158 at risk EG0011 events1 affected159 at risk EG0020 events0 affected34 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected158 at risk EG0010 events0 affected159 at risk EG0020 events0 affected34 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected158 at risk EG0011 events1 affected159 at risk EG0020 events0 affected34 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected158 at risk EG0011 events1 affected159 at risk EG0020 events0 affected34 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected158 at risk EG0011 events1 affected159 at risk EG0020 events0 affected34 at risk
Acute cardiac failure	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected158 at risk EG0010 events0 affected159 at risk EG0020 events0 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0003 events3 affected158 at risk EG00110 events10 affected159 at risk EG0021 events1 affected34 at risk
Glomerular filtration rate decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected158 at risk EG0010 events0 affected159 at risk EG0022 events2 affected34 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0009 events9 affected158 at risk EG00113 events13 affected159 at risk EG0021 events1 affected34 at risk
Polydipsia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0006 events5 affected158 at risk EG0014 events4 affected159 at risk EG0023 events3 affected34 at risk
Polyuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0007 events5 affected158 at risk EG0016 events6 affected159 at risk EG0024 events4 affected34 at risk