Essential Hypertension
Conditions
Brief summary
This integrated assessment consists of two studies, 603A and 603B, to be carried out sequentially in a common study population. Participating subjects informed of the trial design and their consent to participate in both studies were to be obtained in a single consent form. Approximately 680 male or female adult subjects were to be enrolled.
Detailed description
THR-1442-C-603 is an integrated assessment of the potential utility of bexagliflozin tablets, 20 mg for the treatment of essential hypertension. It is composed of two studies, 603A and 603B, measuring effects in a common population. 603A was a multicenter double-blind parallel group placebo-controlled study conducted to determine the placebo-adjusted change from baseline to week 12 in the mean ambulatory systolic blood pressure (SBP) of approximately 680 subjects considered generally representative of the adult hypertensive population in the United States. Secondary endpoints included the placebo-adjusted change from baseline to week 12 of the mean office seated systolic blood pressure, the change to week 12 of the mean ambulatory and mean office seated diastolic blood pressure, the proportion of subjects achieving prespecified goals for absolute systolic and diastolic blood pressure as well as prespecified goals for reduction in systolic and diastolic blood pressure, measured by ambulatory and seated office measurement methodology. A603B was a multicenter double-blind parallel group placebo-controlled randomized withdrawal study conducted to determine the durability of the antihypertensive effect of bexagliflozin tablets, 20 mg, in a population not pre-selected for existing diabetes. All subjects entered a 12 week run-in period during which they self-administered open label bexagliflozin tablets, 20 mg once daily. At week 12 a baseline ambulatory blood pressure monitoring (ABPM) measurement was made, and the subjects were randomized one to one to receive either bexagliflozin tablets, 20 mg or bexagliflozin tablets, placebo. After a 12 week treatment period a second ABPM measurement was made. The primary endpoint was the intergroup difference in the change from baseline in the mean SBP.
Interventions
DRUGBexagliflozin
Bexagliflozin tablet, 20 mg
DRUGPlacebo
Placebo (inactive) tablet to match the active drug
Sponsors
Theracos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
* Study 603A: bexagliflozin tablets, 20 mg or placebo * Study 603B week 1 to week 12: bexagliflozin tablets, 20 mg, open-labeled * Study 603B week 13 to week 24: bexagliflozin tablets, 20 mg or placebo
Intervention model description
The primary endpoint of study 603A is the change from baseline (Day 1) to week 12 in the 24-hour average SBP of the bexagliflozin group compared to the placebo group using a superiority testing at an overall two-sided 0.05 level of significance. The primary endpoint of study 603B is the change from week 12 (cumulative week 24) to week 24 (cumulative week 36) in the 24-hour average SBP in the bexagliflozin group compared to the placebo group using a superiority testing at an overall two-sided 0.05 level of significance.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for randomization a prospective subject was to be: * Male or female of age ≥ 20 years * Diagnosed with essential hypertension and exhibiting an office seated SBP ≥ 140 and \< 180 mm Hg * Unmedicated or prescribed no more than 4 agents for hypertension. Unmedicated subjects were subjects who had never taken medications for hypertension or had not taken any anti-hypertensive medication for at least 3 months. A stable dose meant no change in dose or frequency had taken place in the 4 weeks prior to the screening visit * If female and of childbearing potential, willing to use an adequate method of contraception and to not become pregnant for the duration of the study. * Willing and able to return for all clinic visits and to complete all study-required procedures * Able to self-medicate during the run-in period, omitting no more than one day of dosing * Shown to have a seated SBP ≥ 140 and \< 180 mm Hg * Shown to exhibit a mean 24 h SBP ≥ 135 mm Hg Prospective participants exhibiting any of the following characteristics were to be excluded from the study: * Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young (MODY) * Known history of secondary or malignant hypertension * Seated diastolic blood pressure (DBP) \>110 mm Hg at screening * Taking insulin for diabetes * Prescribed more than 4 anti-hypertension medications * Having a genitourinary tract infection within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within the last 6 months * Having cancer, active or in remission for \< 3 years * History of alcohol or illicit drug abuse in the past 2 years * History of myocardial infarction, stroke or hospitalization for heart failure in the prior 6 months * Previous exposure to bexagliflozin or EGT0001474 * History of hypertensive emergency * History of sodium glucose linked transporter 2 (SGLT2) inhibitor treatment in the last 3 months * Known intolerance or allergy to SGTL2 inhibitors * Any condition, disease, disorder, or clinically relevant laboratory abnormality that, in the opinion of the PI, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment * Pregnancy or nursing * Current participation in another interventional trial or having been exposed to an investigational drug within 30 days or 7 half-lives of screening, whichever is longer * Arm circumference too large or small to allow accurate ambulatory monitoring * History of kidney transplant * Occupational or other lifestyle factors that could hamper the collection of valid ABPM data * Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase \> 1.5 × upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 × ULN * Estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), \< 45 mL/min/1.73 m2 or requiring dialysis * HbA1c \> 9.5% * Positive urine pregnancy test for female subjects of child bearing potential * Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase \> 1.5 × upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 × ULN * eGFR, as calculated by the modification of diet in renal disease study equation (MDRD), \< 45 mL/min/1.73 m2 or requiring dialysis * HbA1c \> 9.5% * Positive urine pregnancy test for female subjects of child bearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12 | Baseline (Day 1) to week 12 | Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared to placebo |
| Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36 | Change from week 24 to week 36 | Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less | Baseline (Day 1) to week 12 | Proportion of subjects who achieve a mean ambulatory systolic blood pressure of 135 mm Hg or less |
| 603A, Change in Seated Office Systolic Blood Pressure | Baseline (Day 1) to week 12 | Placebo-adjusted change in seated office systolic blood pressure |
| 603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less | Baseline (Day 1) to week 12 | Proportion of subjects who achieve a seated office systolic blood pressure of 140 mm Hg or less |
| 603A, Change in Mean Ambulatory Diastolic Blood Pressure | Baseline (Day 1) to week 12 | Placebo-adjusted change in mean ambulatory diastolic blood pressure |
| 603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less | Baseline (Day 1) to week 12 | Proportion of subjects who achieve a mean ambulatory diastolic blood pressure of 87 mm Hg or less |
| 603A, Change in Seated Office Diastolic Blood Pressure | Baseline (Day 1) to week 12 | Placebo-adjusted change in seated office diastolic blood pressure |
| 603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less | Baseline (Day 1) to week 12 | Proportion of subjects who achieve a mean seated office diastolic blood pressure of 90 mm Hg or less |
| 603B, Change in Seated Office Systolic Blood Pressure | Week 12 (cumulative week 24) to Week 24 (cumulative week 36) | Placebo-adjusted change from week 12 to week 24 in seated office systolic blood pressure |
| 603B, Change in Mean Ambulatory Diastolic Blood Pressure | Week 12 (cumulative week 24) to Week 24 (cumulative week 36) | Placebo-adjusted change in mean ambulatory diastolic blood pressure |
| 603B, Change in Seated Office Diastolic Blood Pressure | Week 12 (cumulative week 24) to Week 24 (cumulative week 36) | Placebo-adjusted change from week 12 to week 24 in seated office diastolic blood pressure |
| 603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater | Baseline (Day 1) to week 12 | Proportion of subjects who achieve a reduction of mean ambulatory diastolic blood pressure of 4 mm Hg or greater |
| 603A, Reduction of Mean Ambulatory Systolic Blood Pressure | Baseline (Day 1) to week 12 | Proportion of subjects who achieve a reduction of mean ambulatory systolic blood pressure of 10 mm Hg or greater |
Other
| Measure | Time frame | Description |
|---|---|---|
| Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | Baseline (Day 1) to cumulative week 36 | Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on mean ambulatory systolic and diastolic blood pressure after 12 weeks of bexagliflozin treatment, as well as longer treatment periods, i.e., 24 weeks or 36 weeks of bexagliflozin treatment. |
| Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | Baseline (Day 1) to cumulative week 36 | Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on seated office systolic and diastolic blood pressure over time |
Countries
United States
Participant flow
Pre-assignment details
In the first part of the study (603A), the subjects were randomized to receive bexagliflozin or placebo for 12 weeks.
Participants by arm
| Arm | Count |
|---|---|
| 603A: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. | 334 |
| 603 A: Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for 12 weeks. | 339 |
| 603B: Bexagliflozin Tablets, 20 mg Each eligible subject who have completed 603A including two successful 24-h ABPM sessions at 603A baseline and at week 12, and have completed the 12 weeks open labeled bexagliflozin run-in period with a successful 24-h ABPM session at week 12 of 603B, will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. | 281 |
| 603B: Placebo Tablets Each eligible subject who have completed 603A including two successful 24-h ABPM sessions at 603A baseline and at week 12, and have completed the 12 weeks open labeled bexagliflozin run-in period with a successful 24-h ABPM session at week 12 of 603B, will receive placebo (inactive tablets) once daily for 12 weeks. | 281 |
| Total | 1,235 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 603A: 0-12 Week Study Period | 24 hr ABPM not enough readings | 0 | 1 | 0 | 0 |
| 603A: 0-12 Week Study Period | Adverse Event | 5 | 2 | 0 | 0 |
| 603A: 0-12 Week Study Period | Lack of Efficacy | 1 | 0 | 0 | 0 |
| 603A: 0-12 Week Study Period | Lost to Follow-up | 10 | 9 | 0 | 0 |
| 603A: 0-12 Week Study Period | Physician Decision | 1 | 0 | 0 | 0 |
| 603A: 0-12 Week Study Period | Protocol Violation | 3 | 3 | 0 | 0 |
| 603A: 0-12 Week Study Period | Withdrawal by Subject | 7 | 5 | 0 | 0 |
| 603B: 24-36 Week Study Period | 24 hr ABPM not enough readings | 0 | 0 | 3 | 3 |
| 603B: 24-36 Week Study Period | Adverse Event | 0 | 0 | 3 | 1 |
| 603B: 24-36 Week Study Period | Lost to Follow-up | 0 | 0 | 6 | 6 |
| 603B: 24-36 Week Study Period | Protocol Violation | 0 | 0 | 0 | 2 |
| 603B: 24-36 Week Study Period | Withdrawal by Subject | 0 | 0 | 2 | 3 |
Baseline characteristics
| Characteristic | 603A: Bexagliflozin Tablets, 20 mg | 603 A: Placebo Tablets | Total | 603B: Bexagliflozin Tablets, 20 mg | 603B: Placebo Tablets |
|---|---|---|---|---|---|
| Age, Continuous 603A: 0-12 Week Study Period | 59.4 years STANDARD_DEVIATION 11.32 | 58.3 years STANDARD_DEVIATION 12.06 | 58.9 years STANDARD_DEVIATION 11.71 | — | — |
| Age, Continuous 603B: 12-36 Week Study Period | — | — | 59.6 years STANDARD_DEVIATION 11.58 | 59.9 years STANDARD_DEVIATION 11.39 | 59.2 years STANDARD_DEVIATION 11.78 |
| Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603A: 0-12 Week Study Period; DBP | 85.04 mm Hg STANDARD_DEVIATION 9.24 | 84.97 mm Hg STANDARD_DEVIATION 10.216 | 85.01 mm Hg STANDARD_DEVIATION 9.74 | — | — |
| Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603A: 0-12 Week Study Period; SBP | 147.58 mm Hg STANDARD_DEVIATION 9.64 | 147.48 mm Hg STANDARD_DEVIATION 10.064 | 147.53 mm Hg STANDARD_DEVIATION 9.85 | — | — |
| Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603B: 12-36 Week Study Period; DBP | — | — | 79.39 mm Hg STANDARD_DEVIATION 10.513 | 79.58 mm Hg STANDARD_DEVIATION 10.471 | 79.20 mm Hg STANDARD_DEVIATION 10.571 |
| Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603B: 12-36 Week Study Period; SBP | — | — | 135.96 mm Hg STANDARD_DEVIATION 13.67 | 136.30 mm Hg STANDARD_DEVIATION 13.844 | 135.62 mm Hg STANDARD_DEVIATION 13.51 |
| Body Mass Index 603A: 0-12 Week Study Period | 32.29 kg/m^2 STANDARD_DEVIATION 6.522 | 32.90 kg/m^2 STANDARD_DEVIATION 6.527 | 32.59 kg/m^2 STANDARD_DEVIATION 6.527 | — | — |
| Body Mass Index 603B: 12-36 Week Study Period | — | — | 32.69 kg/m^2 STANDARD_DEVIATION 6.572 | 32.22 kg/m^2 STANDARD_DEVIATION 6.952 | 33.17 kg/m^2 STANDARD_DEVIATION 6.144 |
| Body Weight at Baseline 603A: 0-12 Week Study Period | 95.36 kg STANDARD_DEVIATION 22.643 | 97.47 kg STANDARD_DEVIATION 22.673 | 96.42 kg STANDARD_DEVIATION 22.666 | — | — |
| Body Weight at Baseline 603B: 12-36 Week Study Period | — | — | 96.63 kg STANDARD_DEVIATION 22.721 | 95.71 kg STANDARD_DEVIATION 24.321 | 97.55 kg STANDARD_DEVIATION 21.003 |
| Estimated Glomerular Filtration Rate (eGFR) Mean 603A: 0-12 Week Study Period | 82.64 mL/min/1.73 m^2 STANDARD_DEVIATION 17.438 | 84.42 mL/min/1.73 m^2 STANDARD_DEVIATION 19.71 | 83.53 mL/min/1.73 m^2 STANDARD_DEVIATION 18.625 | — | — |
| Estimated Glomerular Filtration Rate (eGFR) Mean 603B: 12-36 Week Study Period | — | — | 78.35 mL/min/1.73 m^2 STANDARD_DEVIATION 18.908 | 78.75 mL/min/1.73 m^2 STANDARD_DEVIATION 18.971 | 77.95 mL/min/1.73 m^2 STANDARD_DEVIATION 18.871 |
| Ethnicity (NIH/OMB) 603A: 0-12 Week Study Period Hispanic or Latino | 27 Participants | 27 Participants | 54 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) 603A: 0-12 Week Study Period Not Hispanic or Latino | 307 Participants | 312 Participants | 619 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) 603A: 0-12 Week Study Period Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) 603B: 12-36 Week Study Period Hispanic or Latino | 0 Participants | 0 Participants | 46 Participants | 27 Participants | 19 Participants |
| Ethnicity (NIH/OMB) 603B: 12-36 Week Study Period Not Hispanic or Latino | 0 Participants | 0 Participants | 516 Participants | 254 Participants | 262 Participants |
| Ethnicity (NIH/OMB) 603B: 12-36 Week Study Period Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| History of Diabetes 603A: 0-12 Week Study Period No | 251 Participants | 255 Participants | 506 Participants | — | — |
| History of Diabetes 603A: 0-12 Week Study Period Yes | 83 Participants | 84 Participants | 167 Participants | — | — |
| History of Diabetes 603B: 12-36 Week Study Period No | — | — | 418 Participants | 203 Participants | 215 Participants |
| History of Diabetes 603B: 12-36 Week Study Period Yes | — | — | 144 Participants | 78 Participants | 66 Participants |
| Office seated SBP and DBP at baseline 603A: 0-12 Week Study Period; DBP | 91.29 mm Hg STANDARD_DEVIATION 10.269 | 91.48 mm Hg STANDARD_DEVIATION 10.619 | 91.39 mm Hg STANDARD_DEVIATION 10.439 | — | — |
| Office seated SBP and DBP at baseline 603A: 0-12 Week Study Period; SBP | 156.44 mm Hg STANDARD_DEVIATION 10.513 | 155.84 mm Hg STANDARD_DEVIATION 10.335 | 156.14 mm Hg STANDARD_DEVIATION 10.42 | — | — |
| Office seated SBP and DBP at baseline 603B: 12-36 Week Study Period; DBP | — | — | 84.55 mm Hg STANDARD_DEVIATION 10.985 | 84.75 mm Hg STANDARD_DEVIATION 11.623 | 85.28 mm Hg STANDARD_DEVIATION 11.588 |
| Office seated SBP and DBP at baseline 603B: 12-36 Week Study Period; SBP | — | — | 140.94 mm Hg STANDARD_DEVIATION 15.596 | 141.18 mm Hg STANDARD_DEVIATION 16.231 | 140.69 mm Hg STANDARD_DEVIATION 14.96 |
| Race (NIH/OMB) 603A: 0-12 Week Study Period American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603A: 0-12 Week Study Period Asian | 7 Participants | 4 Participants | 11 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603A: 0-12 Week Study Period Black or African American | 94 Participants | 104 Participants | 198 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603A: 0-12 Week Study Period More than one race | 4 Participants | 3 Participants | 7 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603A: 0-12 Week Study Period Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603A: 0-12 Week Study Period Unknown or Not Reported | 9 Participants | 6 Participants | 15 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603A: 0-12 Week Study Period White | 219 Participants | 220 Participants | 439 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period American Indian or Alaska Native | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period Asian | 0 Participants | 0 Participants | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period Black or African American | 0 Participants | 0 Participants | 162 Participants | 92 Participants | 70 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period More than one race | 0 Participants | 0 Participants | 6 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period Unknown or Not Reported | 0 Participants | 0 Participants | 11 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) 603B: 12-36 Week Study Period White | 0 Participants | 0 Participants | 373 Participants | 178 Participants | 195 Participants |
| Sex: Female, Male 603A: 0-12 Week Study Period Female | 127 Participants | 139 Participants | 266 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male 603A: 0-12 Week Study Period Male | 207 Participants | 200 Participants | 407 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male 603B: 12-36 Week Study Period Female | 0 Participants | 0 Participants | 224 Participants | 110 Participants | 114 Participants |
| Sex: Female, Male 603B: 12-36 Week Study Period Male | 0 Participants | 0 Participants | 338 Participants | 171 Participants | 167 Participants |
| Use of any antihypertension medication 603A: 0-12 Week Study Period | 269 Participants | 276 Participants | 545 Participants | — | — |
| Use of any antihypertension medication 603B: 12-36 Week Study Period | — | — | 459 Participants | 233 Participants | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 334 | 0 / 339 | 0 / 281 | 0 / 281 |
| other Total, other adverse events | 94 / 334 | 88 / 339 | 32 / 281 | 37 / 281 |
| serious Total, serious adverse events | 11 / 334 | 10 / 339 | 9 / 281 | 6 / 281 |
Outcome results
Primary
Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12
Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared to placebo
Time frame: Baseline (Day 1) to week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12 | -8.86 mm Hg | Standard Error 0.642 |
| Placebo Tablets | Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12 | -6.15 mm Hg | Standard Error 0.622 |
p-value: 0.002595% CI: [-4.47, -0.96]Covariance
Primary
Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36
Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared placebo
Time frame: Change from week 24 to week 36
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36 | 0.30 mm Hg | Standard Error 0.68 |
| Placebo Tablets | Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36 | 2.74 mm Hg | Standard Error 0.678 |
p-value: 0.011795% CI: [-4.32, -0.54]Covariance
Secondary
603A, Change in Mean Ambulatory Diastolic Blood Pressure
Placebo-adjusted change in mean ambulatory diastolic blood pressure
Time frame: Baseline (Day 1) to week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Change in Mean Ambulatory Diastolic Blood Pressure | -3.92 mm Hg | Standard Error 0.349 |
| Placebo Tablets | 603A, Change in Mean Ambulatory Diastolic Blood Pressure | -3.08 mm Hg | Standard Error 0.337 |
p-value: 0.086395% CI: [-1.79, 0.12]Covariance
Secondary
603A, Change in Seated Office Diastolic Blood Pressure
Placebo-adjusted change in seated office diastolic blood pressure
Time frame: Baseline (Day 1) to week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Change in Seated Office Diastolic Blood Pressure | -4.44 mm Hg | Standard Error 0.504 |
| Placebo Tablets | 603A, Change in Seated Office Diastolic Blood Pressure | -2.13 mm Hg | Standard Error 0.496 |
p-value: 0.001195% CI: [-3.7, -0.92]Covariance
Secondary
603A, Change in Seated Office Systolic Blood Pressure
Placebo-adjusted change in seated office systolic blood pressure
Time frame: Baseline (Day 1) to week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Change in Seated Office Systolic Blood Pressure | -11.24 mm Hg | Standard Error 0.799 |
| Placebo Tablets | 603A, Change in Seated Office Systolic Blood Pressure | -6.61 mm Hg | Standard Error 0.787 |
p-value: <0.000195% CI: [-6.83, -2.42]Covariance
Secondary
603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less
Proportion of subjects who achieve a mean ambulatory diastolic blood pressure of 87 mm Hg or less
Time frame: Baseline (Day 1) to week 12
Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline 24-hour mean SBP/DBP value as a fixed effect covariate.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less | 0.47 Proportion of subjects |
| Placebo Tablets | 603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less | 0.37 Proportion of subjects |
p-value: 0.023295% CI: [1.06, 2.08]Covariance
Secondary
603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less
Proportion of subjects who achieve a mean ambulatory systolic blood pressure of 135 mm Hg or less
Time frame: Baseline (Day 1) to week 12
Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline 24-hour mean SBP/DBP value as a fixed effect covariate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less | 0.40 Proportion of subjects |
| Placebo Tablets | 603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less | 0.29 Proportion of subjects |
p-value: 0.011395% CI: [1.11, 2.3]Covariance
Secondary
603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater
Proportion of subjects who achieve a reduction of mean ambulatory diastolic blood pressure of 4 mm Hg or greater
Time frame: Baseline (Day 1) to week 12
Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline 24-hour mean SBP/DBP value as a fixed effect covariate.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater | 0.88 Proportion of subjects |
| Placebo Tablets | 603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater | 0.80 Proportion of subjects |
p-value: 0.01495% CI: [1.13, 2.91]Covariance
Secondary
603A, Reduction of Mean Ambulatory Systolic Blood Pressure
Proportion of subjects who achieve a reduction of mean ambulatory systolic blood pressure of 10 mm Hg or greater
Time frame: Baseline (Day 1) to week 12
Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline 24-hour mean SBP/DBP value as a fixed effect covariate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Reduction of Mean Ambulatory Systolic Blood Pressure | 0.40 proportion of participants |
| Placebo Tablets | 603A, Reduction of Mean Ambulatory Systolic Blood Pressure | 0.34 proportion of participants |
p-value: 0.131795% CI: [0.92, 1.83]Covariance
Secondary
603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less
Proportion of subjects who achieve a mean seated office diastolic blood pressure of 90 mm Hg or less
Time frame: Baseline (Day 1) to week 12
Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline 24-hour mean SBP/DBP value as a fixed effect covariate.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less | 0.65 Proportion of subjects |
| Placebo Tablets | 603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less | 0.53 Proportion of subjects |
p-value: 0.009495% CI: [1.13, 2.35]Covariance
Secondary
603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less
Proportion of subjects who achieve a seated office systolic blood pressure of 140 mm Hg or less
Time frame: Baseline (Day 1) to week 12
Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline seated office SBP/DBP value as a fixed effect covariate.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less | 0.38 Proportion of subjects |
| Placebo Tablets | 603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less | 0.25 Proportion of subjects |
p-value: 0.000495% CI: [1.32, 2.62]Covariance
Secondary
603B, Change in Mean Ambulatory Diastolic Blood Pressure
Placebo-adjusted change in mean ambulatory diastolic blood pressure
Time frame: Week 12 (cumulative week 24) to Week 24 (cumulative week 36)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603B, Change in Mean Ambulatory Diastolic Blood Pressure | 0.10 mm Hg | Standard Error 0.369 |
| Placebo Tablets | 603B, Change in Mean Ambulatory Diastolic Blood Pressure | 0.94 mm Hg | Standard Error 0.368 |
p-value: 0.108595% CI: [-1.87, 0.19]Covariance
Secondary
603B, Change in Seated Office Diastolic Blood Pressure
Placebo-adjusted change from week 12 to week 24 in seated office diastolic blood pressure
Time frame: Week 12 (cumulative week 24) to Week 24 (cumulative week 36)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603B, Change in Seated Office Diastolic Blood Pressure | 0.51 mm Hg | Standard Error 0.507 |
| Placebo Tablets | 603B, Change in Seated Office Diastolic Blood Pressure | 1.76 mm Hg | Standard Error 0.514 |
p-value: 0.083795% CI: [-2.67, 0.17]Covariance
Secondary
603B, Change in Seated Office Systolic Blood Pressure
Placebo-adjusted change from week 12 to week 24 in seated office systolic blood pressure
Time frame: Week 12 (cumulative week 24) to Week 24 (cumulative week 36)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | 603B, Change in Seated Office Systolic Blood Pressure | 1.98 mm Hg | Standard Error 0.846 |
| Placebo Tablets | 603B, Change in Seated Office Systolic Blood Pressure | 5.18 mm Hg | Standard Error 0.859 |
p-value: 0.008395% CI: [-5.57, -0.83]Covariance
Other Pre-specified
Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure
Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on mean ambulatory systolic and diastolic blood pressure after 12 weeks of bexagliflozin treatment, as well as longer treatment periods, i.e., 24 weeks or 36 weeks of bexagliflozin treatment.
Time frame: Baseline (Day 1) to cumulative week 36
Population: Number of subjects with baseline and value after specified weeks of exposure to Bexagliflozin
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | 12 Weeks | -7.595 mm Hg |
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | 24 Weeks | -9.262 mm Hg |
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | 36 Weeks | -12.454 mm Hg |
| Placebo Tablets | Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | 12 Weeks | -3.269 mm Hg |
| Placebo Tablets | Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | 24 Weeks | -4.044 mm Hg |
| Placebo Tablets | Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure | 36 Weeks | -5.566 mm Hg |
Other Pre-specified
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure
Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on seated office systolic and diastolic blood pressure over time
Time frame: Baseline (Day 1) to cumulative week 36
Population: Number of subjects with baseline and value after specified weeks of exposure to Bexagliflozin
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 24 Weeks | -12.53 mm Hg | Standard Deviation 18.83 |
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 6 Weeks | -8.43 mm Hg | Standard Deviation 16.399 |
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 12 Weeks | -9.91 mm Hg | Standard Deviation 15.777 |
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 18 Weeks | -14.46 mm Hg | Standard Deviation 16 |
| Bexagliflozin Tablets, 20 mg | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 36 Weeks | -15.71 mm Hg | Standard Deviation 16.975 |
| Placebo Tablets | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 36 Weeks | -6.47 mm Hg | Standard Deviation 9.933 |
| Placebo Tablets | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 18 Weeks | -5.87 mm Hg | Standard Deviation 9.282 |
| Placebo Tablets | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 6 Weeks | -4.50 mm Hg | Standard Deviation 9.534 |
| Placebo Tablets | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 24 Weeks | -4.92 mm Hg | Standard Deviation 10.91 |
| Placebo Tablets | Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure | 12 Weeks | -4.10 mm Hg | Standard Deviation 9.716 |