Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to investigate the effect of bexagliflozin in lowering hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM) and increased risk of cardiovascular adverse events. The data from this study will be combined with the data from other bexagliflozin studies in a meta-analysis of CV safety outcomes.
Detailed description
Approximately 130 investigative sites globally are planned to participate in this study. An estimated 1650 subjects with inadequately controlled T2DM and an elevated risk of cardiovascular adverse events will be randomized to bexagliflozin tablets, 20 mg, or placebo in a ratio of 2:1 in addition to the background anti-diabetic medications. The study is an event-driven trial. The treatment period will end when the last randomized subject has completed at least 52 weeks of treatment and a total of at least 134 subjects have experienced a cardiac event.
Interventions
DRUGBexagliflozin
20 mg, tablet
DRUGPlacebo
20 mg tablet to match active comparator
Sponsors
Theracos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of T2DM * Subjects who have had a stable treatment regimen for T2DM for the past 3 months * Subjects who present with at least one of the following 3 histories: Group 1: A history of atherosclerotic vascular disease Group 2: A history of heart failure Group 3: Age ≥ 55 years with diabetes for ≥ 10 years, uncontrolled hypertension, currently smoking, reduced kidney function, or cholesterol problems
Exclusion criteria
* Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young * History of genitourinary tract infections * Evidence of abnormal liver function * History of MI, stroke or hospitalization for heart failure in the past 3 months * Prior kidney transplant or evidence of kidney problems * Prior or planned pace maker implantation * Pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 24 | 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 increased risk of cardiovascular adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin | 24 weeks | To evaluate the effect of 20 mg bexagliflozin on the change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes |
| Change in Body Weight From Baseline to Week 48 | 48 weeks | To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48 in randomized subjects with a BMI ≥ 25 kg/m2 compared to placebo |
| Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline | 24 weeks | To evaluate the effect of 20 mg bexagliflozin on the change in systolic blood pressure (SBP) from baseline to week 24 in subjects with baseline systolic blood pressure ≥ 140 mmHg compared to placebo |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline Over Time | Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168 | To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c from baseline versus placebo over time up to 168 weeks |
| Proportion of Participants With Incidence of Hospitalization for Heart Failure | Duration of study (168 weeks) | To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline |
| Change in Fasting Plasma Glucose Over Time | Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168 | To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time up to 168 weeks |
| Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification | 24 week | To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period |
| Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent | 24 weeks | To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period |
Countries
Canada, Czechia, Denmark, Mexico, Netherlands, Poland, Russia, South Korea, Taiwan, United States
Participant flow
Recruitment details
A total of 1700 patients were recruited from 10 countries: Canada, Czech Republic, Demark, Republic of Korea, Mexico, the Netherlands, Poland, Russian Federation, Taiwan, and the United States.
Pre-assignment details
Subjects ≥ 40 years old with inadequately controlled T2DM with HbA1c between 7.5% (7.0% since protocol version 8) and 11% on stable medications and elevated risk for CV adverse events were enrolled. All subjects must belong to 1 of 3 CV risk groups to be eligible. All eligible subjects took placebo during 13 ± 2 days run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin 20 mg once daily for the duration of the study.
Bexagliflozin: 20 mg, tablet | 1,133 |
| Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for the duration of the study.
Placebo: 20 mg tablet to match active comparator | 567 |
| Total | 1,700 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed the Study | Adverse Event | 14 | 5 |
| Completed the Study | Death | 39 | 25 |
| Completed the Study | Lost to Follow-up | 31 | 23 |
| Completed the Study | Physician Decision | 6 | 0 |
| Completed the Study | Protocol Violation | 2 | 1 |
| Completed the Study | The subject was randomized, but did not take any investigational product | 1 | 0 |
| Completed the Study | Withdrawal by Subject | 53 | 31 |
| Completed the Study Through Week 24 | Adverse Event | 9 | 3 |
| Completed the Study Through Week 24 | Death | 7 | 7 |
| Completed the Study Through Week 24 | Lost to Follow-up | 8 | 1 |
| Completed the Study Through Week 24 | Physician Decision | 1 | 0 |
| Completed the Study Through Week 24 | Protocol Violation | 1 | 1 |
| Completed the Study Through Week 24 | The subject was randomized, but did not take any investigational product | 1 | 0 |
| Completed the Study Through Week 24 | Withdrawal by Subject | 17 | 13 |
Baseline characteristics
| Characteristic | Total | Bexagliflozin Tablets, 20 mg | Placebo Tablets |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 862 Participants | 571 Participants | 291 Participants |
| Age, Categorical Between 18 and 65 years | 838 Participants | 562 Participants | 276 Participants |
| Age, Continuous | 64.4 years STANDARD_DEVIATION 7.96 | 64.4 years STANDARD_DEVIATION 7.94 | 64.6 years STANDARD_DEVIATION 8.01 |
| Body Mass Index | 32.62 kg/m^2 STANDARD_DEVIATION 5.968 | 32.80 kg/m^2 STANDARD_DEVIATION 6.068 | 32.24 kg/m^2 STANDARD_DEVIATION 5.751 |
| Body Mass Index Categories BMI < 25 kg/m^2 | 131 Participants | 86 Participants | 45 Participants |
| Body Mass Index Categories BMI >= 25 kg/m^2 | 1569 Participants | 1047 Participants | 522 Participants |
| Body Weight | 93.94 kg STANDARD_DEVIATION 20.745 | 94.59 kg STANDARD_DEVIATION 21.87 | 92.62 kg STANDARD_DEVIATION 19.999 |
| Cardiovascular Risk Groups Group 1: History of atherosclerotic vascular disease | 1065 Participants | 703 Participants | 362 Participants |
| Cardiovascular Risk Groups Group 2: History of heart failure | 246 Participants | 166 Participants | 80 Participants |
| Cardiovascular Risk Groups Group 3: Age >= 55 years with > 2 risk factors | 389 Participants | 264 Participants | 125 Participants |
| Diastolic Blood Pressure | 77.0 mmHg STANDARD_DEVIATION 10.01 | 77.1 mmHg STANDARD_DEVIATION 9.94 | 76.8 mmHg STANDARD_DEVIATION 10.16 |
| Duration of Diabetes from Diagnosis to the date of informed consent | 14.99 years STANDARD_DEVIATION 8.845 | 14.87 years STANDARD_DEVIATION 8.635 | 15.23 years STANDARD_DEVIATION 9.253 |
| eGFR at Screening | 77.88 mL/min/1.73 m^2 STANDARD_DEVIATION 19.529 | 77.93 mL/min/1.73 m^2 STANDARD_DEVIATION 19.475 | 77.76 mL/min/1.73 m^2 STANDARD_DEVIATION 19.653 |
| eGFR group < 60 mL/min/1.73 m^2 | 334 Participants | 225 Participants | 109 Participants |
| eGFR group >= 60 mL/min/1.73 m^2 | 1366 Participants | 908 Participants | 458 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 259 Participants | 166 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1441 Participants | 967 Participants | 474 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 8.32 % of HbA1c STANDARD_DEVIATION 0.913 | 8.32 % of HbA1c STANDARD_DEVIATION 0.897 | 8.33 % of HbA1c STANDARD_DEVIATION 0.944 |
| HbA1c group <= 8.5% | 1078 Participants | 716 Participants | 362 Participants |
| HbA1c group > 8.5% | 622 Participants | 417 Participants | 205 Participants |
| Insulin Use at Baseline No | 798 Participants | 523 Participants | 275 Participants |
| Insulin Use at Baseline Yes | 902 Participants | 610 Participants | 292 Participants |
| Left Ventricular Ejection Fraction | 49.8 % of Left Ventricular Ejection Fraction STANDARD_DEVIATION 13.74 | 49.2 % of Left Ventricular Ejection Fraction STANDARD_DEVIATION 14.13 | 50.8 % of Left Ventricular Ejection Fraction STANDARD_DEVIATION 12.95 |
| NT-proBNP | 346.1 pmol/L STANDARD_DEVIATION 661.93 | 391.9 pmol/L STANDARD_DEVIATION 760.75 | 264.0 pmol/L STANDARD_DEVIATION 427.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 152 Participants | 98 Participants | 54 Participants |
| Race (NIH/OMB) Asian | 163 Participants | 108 Participants | 55 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants | 46 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1309 Participants | 879 Participants | 430 Participants |
| Region of Enrollment Canada | 91 participants | 67 participants | 24 participants |
| Region of Enrollment Czechia | 170 participants | 118 participants | 52 participants |
| Region of Enrollment Denmark | 27 participants | 17 participants | 10 participants |
| Region of Enrollment Mexico | 183 participants | 121 participants | 62 participants |
| Region of Enrollment Netherlands | 54 participants | 36 participants | 18 participants |
| Region of Enrollment Poland | 293 participants | 196 participants | 97 participants |
| Region of Enrollment Russia | 140 participants | 87 participants | 53 participants |
| Region of Enrollment South Korea | 74 participants | 48 participants | 26 participants |
| Region of Enrollment Taiwan | 66 participants | 46 participants | 20 participants |
| Region of Enrollment United States | 602 participants | 397 participants | 205 participants |
| Sex: Female, Male Female | 518 Participants | 341 Participants | 177 Participants |
| Sex: Female, Male Male | 1182 Participants | 792 Participants | 390 Participants |
| Systolic Blood Pressure | 134.0 mmHg STANDARD_DEVIATION 16.21 | 134.2 mmHg STANDARD_DEVIATION 16.24 | 133.7 mmHg STANDARD_DEVIATION 16.18 |
| Systolic Blood Pressure Groups < 140 mmHg | 1037 Participants | 685 Participants | 352 Participants |
| Systolic Blood Pressure Groups >= 140 mmHg | 663 Participants | 448 Participants | 215 Participants |
| Use of Anti-Diabetic Treatment at Baseline No | 11 Participants | 8 Participants | 3 Participants |
| Use of Anti-Diabetic Treatment at Baseline Yes | 1689 Participants | 1125 Participants | 564 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 39 / 1,132 | 26 / 567 |
| other Total, other adverse events | 739 / 1,132 | 386 / 567 |
| serious Total, serious adverse events | 373 / 1,132 | 208 / 567 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 24
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 increased risk of cardiovascular adverse events.
Time frame: 24 weeks
Population: Number of subjects with a value at baseline and at Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline to Week 24 | -0.85 percentage of glycated hemoglobin |
| Placebo Tablets | Change in HbA1c From Baseline to Week 24 | -0.37 percentage of glycated hemoglobin |
Comparison: The null hypothesis for the primary endpoint was that the mean change in HbA1c from baseline to Week 24 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.56, -0.39]Mixed-effects repeated measures
Secondary
Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin
To evaluate the effect of 20 mg bexagliflozin on the change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes
Time frame: 24 weeks
Population: Number of subjects with a value at baseline and at week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin | -0.84 Percentage of HbA1c |
| Placebo Tablets | Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin | -0.32 Percentage of HbA1c |
Comparison: The null hypothesis for the secondary endpoint was that the mean change in HbA1c from baseline to Week 24 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.65, -0.4]Mixed-effects repeated measures
Secondary
Change in Body Weight From Baseline to Week 48
To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48 in randomized subjects with a BMI ≥ 25 kg/m2 compared to placebo
Time frame: 48 weeks
Population: Number of subjects with a value at baseline and at Week 48 is included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change in Body Weight From Baseline to Week 48 | -3.03 kg |
| Placebo Tablets | Change in Body Weight From Baseline to Week 48 | -0.38 kg |
Comparison: The null hypothesis for the secondary endpoint was that the mean change in body weight from baseline to Week 48 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-3.07, -2.24]Mixed-effects repeated measures
Secondary
Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline
To evaluate the effect of 20 mg bexagliflozin on the change in systolic blood pressure (SBP) from baseline to week 24 in subjects with baseline systolic blood pressure ≥ 140 mmHg compared to placebo
Time frame: 24 weeks
Population: Number of subjects with a value at baseline and at week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline | -9.83 mm Hg |
| Placebo Tablets | Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline | -6.87 mm Hg |
Comparison: The null hypothesis for the secondary endpoint was that the mean change in systolic blood pressure from baseline to Week 24 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: 0.011295% CI: [-5.51, -0.42]Mixed-effects repeated measures
Other Pre-specified
Change in Fasting Plasma Glucose Over Time
To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time up to 168 weeks
Time frame: Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168
Population: Number of subjects with a value at baseline and at the specified visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 6 | -1.28 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 12 | -1.33 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 24 | -1.43 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 36 | -1.21 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 48 | -1.36 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 72 | -1.14 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 96 | -1.16 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 120 | -0.90 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 144 | -1.03 mmol/L |
| Bexagliflozin Tablets, 20 mg | Change in Fasting Plasma Glucose Over Time | Week 168 | -1.06 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 120 | 0.25 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 6 | 0.07 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 72 | -0.15 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 12 | 0.06 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 168 | -0.55 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 24 | -0.05 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 96 | 0.04 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 36 | -0.06 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 144 | -0.40 mmol/L |
| Placebo Tablets | Change in Fasting Plasma Glucose Over Time | Week 48 | -0.12 mmol/L |
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 6 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.55, -1.15]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 12 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.61, -1.18]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 24 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.61, -1.16]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 36 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.41, -0.89]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 48 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.48, -0.98]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 72 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.27, -0.72]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 96 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.5, -0.9]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 120 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-1.49, -0.82]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 144 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: 0.000895% CI: [-1.01, -0.24]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in FPG from baseline to Week 168 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: 0.046295% CI: [-1.09, 0.08]Mixed-effects repeated measures
Other Pre-specified
Change in HbA1c From Baseline Over Time
To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c from baseline versus placebo over time up to 168 weeks
Time frame: Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168
Population: Number of subjects with a value at baseline and at the specified visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 72 | -0.76 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 24 | -0.84 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 96 | -0.68 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 12 | -0.89 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 120 | -0.65 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 36 | -0.86 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 144 | -0.62 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 48 | -0.84 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 168 | -0.56 Percentage of HbA1c |
| Bexagliflozin Tablets, 20 mg | Change in HbA1c From Baseline Over Time | Week 6 | -0.69 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 168 | -0.29 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 6 | -0.24 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 12 | -0.34 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 24 | -0.37 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 48 | -0.38 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 72 | -0.34 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 96 | -0.29 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 120 | -0.22 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 144 | -0.23 Percentage of HbA1c |
| Placebo Tablets | Change in HbA1c From Baseline Over Time | Week 36 | -0.39 Percentage of HbA1c |
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 6 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.5, -0.39]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 12 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.63, -0.49]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 24 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.56, -0.38]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 36 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.56, -0.38]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 48 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.56, -0.37]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 72 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.54, -0.31]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 96 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.51, -0.27]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 120 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.56, -0.3]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 144 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: <0.000195% CI: [-0.54, -0.23]Mixed-effects repeated measures
Comparison: The null hypothesis for the exploratory endpoint was that the mean change in HbA1c from baseline to Week 168 in the bexagliflozin arm would be equal to or greater than the mean change in the placebo arm.p-value: 0.004595% CI: [-0.47, -0.07]Mixed-effects repeated measures
Other Pre-specified
Proportion of Participants With Incidence of Hospitalization for Heart Failure
To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline
Time frame: Duration of study (168 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Proportion of Participants With Incidence of Hospitalization for Heart Failure | 0.01 Proportion of participants |
| Placebo Tablets | Proportion of Participants With Incidence of Hospitalization for Heart Failure | 0.02 Proportion of participants |
| Subjects With HF History: Bexagliflozin Tablets, 20 mg | Proportion of Participants With Incidence of Hospitalization for Heart Failure | 0.05 Proportion of participants |
| Subjects With HF History: Placebo | Proportion of Participants With Incidence of Hospitalization for Heart Failure | 0.09 Proportion of participants |
p-value: 0.027295% CI: [0.22, 1.01]Regression, Logistic
p-value: 0.075795% CI: [0.34, 1.18]Regression, Cox
p-value: 0.080395% CI: [0.33, 1.2]Regression, Logistic
p-value: 0.027395% CI: [0.23, 1.01]Regression, Cox
Other Pre-specified
Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification
To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period
Time frame: 24 week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification | 0.06 Proportion of participants |
| Placebo Tablets | Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification | 0.18 Proportion of participants |
p-value: <0.000195% CI: [0.22, 0.41]Regression, Logistic
Other Pre-specified
Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification
To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study period
Time frame: Duration of study (168 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification | 0.06 Proportion of participants |
| Placebo Tablets | Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification | 0.18 Proportion of participants |
p-value: <0.000195% CI: [0.35, 0.49]Regression, Cox
Other Pre-specified
Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent
To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent | 0.09 Proportion of participants |
| Placebo Tablets | Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent | 0.05 Proportion of participants |
p-value: 0.000595% CI: [1.33, 3.11]Regression, Logistic
Other Pre-specified
Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent
To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study
Time frame: Duration of study (168 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent | 0.09 Proportion of participants |
| Placebo Tablets | Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent | 0.05 Proportion of participants |
p-value: <0.000195% CI: [1.4, 2.38]Regression, Cox