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An Integrated Assessment of the Safety and Effectiveness of Bexagliflozin for the Management of Essential Hypertension

Sponsor
Theracos (Industry)
Overall Status
Completed
CT.gov ID
NCT03514641
Collaborator
(none)
673
Enrollment
87
Locations
4
Arms
13.4
Actual Duration (Months)
7.7
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
673 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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.
Masking:
Quadruple (Participant, Care Provider, 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
Primary Purpose:
Treatment
Official Title:
An Integrated Assessment of the Safety and Effectiveness of Bexagliflozin Tablets, 20 mg, for the Management of Essential Hypertension
Actual Study Start Date :
Oct 18, 2017
Actual Primary Completion Date :
Nov 30, 2018
Actual Study Completion Date :
Nov 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Other: Sequence 1

Period 1: Placebo Period 2: Bexagliflozin Period 3: Bexagliflozin

Drug: Bexagliflozin
Bexagliflozin tablet, 20 mg
Other Names:
  • EGT0001442

    • Drug: Placebo
    Placebo (inactive) tablet to match the active drug
    Other: Sequence 2

    Period 1: Placebo Period 2: Bexagliflozin Period 3: Placebo

    Drug: Bexagliflozin
    Bexagliflozin tablet, 20 mg
    Other Names:
  • EGT0001442

    • Drug: Placebo
    Placebo (inactive) tablet to match the active drug
    Other: Sequence 3

    Period 1: Bexagliflozin Period 2: Bexagliflozin Period 3: Bexagliflozin

    Drug: Bexagliflozin
    Bexagliflozin tablet, 20 mg
    Other Names:
  • EGT0001442

    		•
    Other: Sequence 4

    Period 1: Bexagliflozin Period 2: Bexagliflozin Period 3: Placebo

    Drug: Bexagliflozin
    Bexagliflozin tablet, 20 mg
    Other Names:
  • EGT0001442

    • Drug: Placebo
    Placebo (inactive) tablet to match the active drug

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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 Outcome Measures

    1. 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

    2. 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

    3. 603A, Change in Seated Office Systolic Blood Pressure [Baseline (Day 1) to week 12]

      Placebo-adjusted change in seated office systolic blood pressure

    4. 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

    5. 603A, Change in Mean Ambulatory Diastolic Blood Pressure [Baseline (Day 1) to week 12]

      Placebo-adjusted change in mean ambulatory diastolic blood pressure

    6. 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

    7. 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

    8. 603A, Change in Seated Office Diastolic Blood Pressure [Baseline (Day 1) to week 12]

      Placebo-adjusted change in seated office diastolic blood pressure

    9. 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

    10. 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

    11. 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

    12. 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

    Other Outcome Measures

    1. 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.

    2. 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

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Research Site Birmingham Alabama United States 35205
    2 Clinical Research Site Birmingham Alabama United States 35211
    3 Clinical Research Site Birmingham Alabama United States 35242
    4 Clinical Research Site Foley Alabama United States 36535
    5 Clinical Research Site Gulf Shores Alabama United States 36542
    6 Clinical Research Site Glendale Arizona United States 85306
    7 Clinical Research Site Mesa Arizona United States 85206
    8 Clinical Research Site Phoenix Arizona United States 85020
    9 Clinical Research Site Tucson Arizona United States 85741
    10 Clinical Research Site Anaheim California United States 92801
    11 Clinical Research Site Bellflower California United States 90706
    12 Clinical Research Site Fair Oaks California United States 95628
    13 Clinical Research Site Fresno California United States 93702
    14 Clinical Research Site Lincoln California United States 95648
    15 Clinical Research Site Los Angeles California United States 90057
    16 Clinical Research Site San Gabriel California United States 91776
    17 Clinical Research Site Santa Rosa California United States 95405
    18 Clinical Research Site Upland California United States 91786
    19 Clinical Research Site Colorado Springs Colorado United States 80909
    20 Clinical Research Site Colorado Springs Colorado United States 80918
    21 Clinical Research Site Denver Colorado United States 80246
    22 Clinical Research Site Golden Colorado United States 80401
    23 Clinical Research Site Stamford Connecticut United States 06905
    24 Clinical Research Site Decatur Georgia United States 30030
    25 Clinical Research Site Decatur Georgia United States 30032
    26 Clinical Research Site Lithonia Georgia United States 30058
    27 Clinical Research Site Chicago Illinois United States 60602
    28 Clinical Research Site Chicago Illinois United States 60611
    29 Clinical Research Site Chicago Illinois United States 60616
    30 Clinical Research Site Avon Indiana United States 46123
    31 Clinical Research Site Evansville Indiana United States 47714
    32 Clinical Research Site Indianapolis Indiana United States 46260
    33 Clinical Research Site Council Bluffs Iowa United States 51503
    34 Clinical Research Site Prairie Village Kansas United States 66208
    35 Clinical Research Site Lexington Kentucky United States 40503
    36 Clinical Research Site Paducah Kentucky United States 42003
    37 Clinical Research Site Versailles Kentucky United States 40383
    38 Clinical Research Site New Orleans Louisiana United States 70115
    39 Clinical Research Site Auburn Maine United States 04210
    40 Clinical Research Site Silver Spring Maryland United States 20910
    41 Clinical Research Site Edina Minnesota United States 55435
    42 Clinical Research Site Bridgeton Missouri United States 63044
    43 Clinical Research Site Saint Louis Missouri United States 63141
    44 Clinical Research Site Henderson Nevada United States 89074
    45 Clinical Research Site Las Vegas Nevada United States 89128
    46 Clinical Research Site Trenton New Jersey United States 08611
    47 Clinical Research Site Albuquerque New Mexico United States 87102
    48 Clinical Research Site Bronx New York United States 10455
    49 Clinical Research Site Brooklyn New York United States 11230
    50 Clinical Research Site Hartsdale New York United States 10530
    51 Clinical Research Site Shelby North Carolina United States 28150
    52 Clinical Research Site Akron Ohio United States 44311
    53 Clinical Research Site Cincinnati Ohio United States 45236
    54 Clinical Research Site Cincinnati Ohio United States 45245
    55 Clinical Research Site Columbus Ohio United States 43213
    56 Clinical Research Site Dayton Ohio United States 45439
    57 Clinical Research Site Dublin Ohio United States 43215
    58 Clinical Research Site Grove City Ohio United States 43214
    59 Clinical Research Site Lyndhurst Ohio United States 44124
    60 Clinical Research Site Edmond Oklahoma United States 73034
    61 Clinical Research Site Oklahoma City Oklahoma United States 73119
    62 Clinical Research Site Portland Oregon United States 97239
    63 Clinical Research Site Altoona Pennsylvania United States 16602
    64 Clinical Research Site Hatboro Pennsylvania United States 19040
    65 Clinical Research Site Lincoln Rhode Island United States 02865
    66 Clinical Research Site 2 Anderson South Carolina United States 29621
    67 Clinical Research Site Anderson South Carolina United States 29621
    68 Clinical Research Site Greer South Carolina United States 29650
    69 Clinical Research Site Kingsport Tennessee United States 37660
    70 Clinical Research Site Knoxville Tennessee United States 37909
    71 Clinical Research Site Arlington Texas United States 76014
    72 Clinical Research Site Dallas Texas United States 75231
    73 Clinical Research Site Houston Texas United States 77070
    74 Clinical Research Site Kingwood Texas United States 77339
    75 Clinical Research Site Mesquite Texas United States 75143
    76 Clinical Research Site Plano Texas United States 75093
    77 Clinical Research Site San Antonio Texas United States 78229
    78 Clinical Research Site Tomball Texas United States 77375
    79 Clinical Research Site Layton Utah United States 84041
    80 Clinical Research Site Murray Utah United States 84123
    81 Clinical Research Site West Jordan Utah United States 84088
    82 Clinical Research Site Arlington Virginia United States 22207
    83 Clinical Research Site Burke Virginia United States 22015
    84 Clinical Research Site Charlottesville Virginia United States 22911
    85 Clinical Research Site Danville Virginia United States 24541
    86 Clinical Research Site Manassas Virginia United States 20110
    87 Clinical Research Site Tacoma Washington United States 98405

    Sponsors and Collaborators

    • Theracos

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Theracos
    ClinicalTrials.gov Identifier:
    NCT03514641
    Other Study ID Numbers:
    • THR-1442-C-603
    First Posted:
    May 2, 2018
    Last Update Posted:
    Sep 21, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hypertension
    Essential Hypertension
    Bexagliflozin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail In the first part of the study (603A), the subjects were randomized to receive bexagliflozin or placebo for 12 weeks.
    Arm/Group Title 603A: Bexagliflozin Tablets, 20 mg 603A: Placebo Tablets 603B: Bexagliflozin Tablets, 20 mg 603B: Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks Each subject will receive placebo (inactive tablet) once daily for 12 weeks. Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks from week 24 to week 36 (cumulative) Each subject will receive placebo (inactive tablet) once daily for 12 weeks from week 24 to week 36 (cumulative)
    Period Title: 603A: 0-12 Week Study Period
    STARTED 334 339 0 0
    COMPLETED 307 319 0 0
    NOT COMPLETED 27 20 0 0
    Period Title: 603A: 0-12 Week Study Period
    STARTED 0 0 281 281
    COMPLETED 0 0 267 266
    NOT COMPLETED 0 0 14 15

    Baseline Characteristics

    Arm/Group Title 603A: Bexagliflozin Tablets, 20 mg 603 A: Placebo Tablets 603B: Bexagliflozin Tablets, 20 mg 603B: Placebo Tablets Total
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks. 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. 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. Total of all reporting groups
    Overall Participants 334 339 281 281 1235
    Age (years) [Mean (Standard Deviation) ]
    603A: 0-12 Week Study Period
    59.4
    (11.32)
    58.3
    (12.06)
    58.9
    (11.71)
    603B: 12-36 Week Study Period
    59.9
    (11.39)
    59.2
    (11.78)
    59.6
    (11.58)
    Sex: Female, Male (Count of Participants)
    Female
    127
    38%
    139
    41%
    0
    0%
    0
    0%
    266
    21.5%
    Male
    207
    62%
    200
    59%
    0
    0%
    0
    0%
    407
    33%
    Female
    0
    0%
    0
    0%
    110
    39.1%
    114
    40.6%
    224
    18.1%
    Male
    0
    0%
    0
    0%
    171
    60.9%
    167
    59.4%
    338
    27.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    27
    8.1%
    27
    8%
    0
    0%
    0
    0%
    54
    4.4%
    Not Hispanic or Latino
    307
    91.9%
    312
    92%
    0
    0%
    0
    0%
    619
    50.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Hispanic or Latino
    0
    0%
    0
    0%
    27
    9.6%
    19
    6.8%
    46
    3.7%
    Not Hispanic or Latino
    0
    0%
    0
    0%
    254
    90.4%
    262
    93.2%
    516
    41.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    2
    0.6%
    0
    0%
    0
    0%
    2
    0.2%
    Asian
    7
    2.1%
    4
    1.2%
    0
    0%
    0
    0%
    11
    0.9%
    Native Hawaiian or Other Pacific Islander
    1
    0.3%
    0
    0%
    0
    0%
    0
    0%
    1
    0.1%
    Black or African American
    94
    28.1%
    104
    30.7%
    0
    0%
    0
    0%
    198
    16%
    White
    219
    65.6%
    220
    64.9%
    0
    0%
    0
    0%
    439
    35.5%
    More than one race
    4
    1.2%
    3
    0.9%
    0
    0%
    0
    0%
    7
    0.6%
    Unknown or Not Reported
    9
    2.7%
    6
    1.8%
    0
    0%
    0
    0%
    15
    1.2%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    1
    0.4%
    1
    0.4%
    2
    0.2%
    Asian
    0
    0%
    0
    0%
    4
    1.4%
    4
    1.4%
    8
    0.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    92
    32.7%
    70
    24.9%
    162
    13.1%
    White
    0
    0%
    0
    0%
    178
    63.3%
    195
    69.4%
    373
    30.2%
    More than one race
    0
    0%
    0
    0%
    2
    0.7%
    4
    1.4%
    6
    0.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    4
    1.4%
    7
    2.5%
    11
    0.9%
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    603A: 0-12 Week Study Period
    32.29
    (6.522)
    32.90
    (6.527)
    32.59
    (6.527)
    603B: 12-36 Week Study Period
    32.22
    (6.952)
    33.17
    (6.144)
    32.69
    (6.572)
    Body Weight at Baseline (kg) [Mean (Standard Deviation) ]
    603A: 0-12 Week Study Period
    95.36
    (22.643)
    97.47
    (22.673)
    96.42
    (22.666)
    603B: 12-36 Week Study Period
    95.71
    (24.321)
    97.55
    (21.003)
    96.63
    (22.721)
    History of Diabetes (Count of Participants)
    Yes
    83
    24.9%
    84
    24.8%
    167
    59.4%
    No
    251
    75.1%
    255
    75.2%
    506
    180.1%
    Yes
    78
    23.4%
    66
    19.5%
    144
    51.2%
    No
    203
    60.8%
    215
    63.4%
    418
    148.8%
    Use of any antihypertension medication (Count of Participants)
    603A: 0-12 Week Study Period
    269
    80.5%
    276
    81.4%
    545
    194%
    603B: 12-36 Week Study Period
    233
    69.8%
    226
    66.7%
    459
    163.3%
    Estimated Glomerular Filtration Rate (eGFR) Mean (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
    603A: 0-12 Week Study Period
    82.64
    (17.438)
    84.42
    (19.710)
    83.53
    (18.625)
    603B: 12-36 Week Study Period
    78.75
    (18.971)
    77.95
    (18.871)
    78.35
    (18.908)
    Ambulatory Blood Pressure Monitoring (ABPM) at baseline (mm Hg) [Mean (Standard Deviation) ]
    603A: 0-12 Week Study Period; SBP
    147.58
    (9.640)
    147.48
    (10.064)
    147.53
    (9.850)
    603A: 0-12 Week Study Period; DBP
    85.04
    (9.240)
    84.97
    (10.216)
    85.01
    (9.740)
    603B: 12-36 Week Study Period; SBP
    136.30
    (13.844)
    135.62
    (13.510)
    135.96
    (13.67)
    603B: 12-36 Week Study Period; DBP
    79.58
    (10.471)
    79.20
    (10.571)
    79.39
    (10.513)
    Office seated SBP and DBP at baseline (mm Hg) [Mean (Standard Deviation) ]
    603A: 0-12 Week Study Period; SBP
    156.44
    (10.513)
    155.84
    (10.335)
    156.14
    (10.420)
    603A: 0-12 Week Study Period; DBP
    91.29
    (10.269)
    91.48
    (10.619)
    91.39
    (10.439)
    603B: 12-36 Week Study Period; SBP
    141.18
    (16.231)
    140.69
    (14.960)
    140.94
    (15.596)
    603B: 12-36 Week Study Period; DBP
    84.75
    (11.623)
    85.28
    (11.588)
    84.55
    (10.985)

    Outcome Measures

    1. Primary Outcome
    Title Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12
    Description Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared to placebo
    Time Frame Baseline (Day 1) to week 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (Standard Error) [mm Hg]
    -8.86
    (0.642)
    -6.15
    (0.622)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0025
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter LS Means difference
    Estimated Value -2.72
    Confidence Interval (2-Sided) 95%
    -4.47 to -0.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36
    Description Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared placebo
    Time Frame Change from week 24 to week 36

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 281 281
    Least Squares Mean (Standard Error) [mm Hg]
    0.30
    (0.680)
    2.74
    (0.678)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0117
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.43
    Confidence Interval (2-Sided) 95%
    -4.32 to -0.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title 603A, Reduction of Mean Ambulatory Systolic Blood Pressure
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Number (95% Confidence Interval) [proportion of participants]
    0.40
    0.1%
    0.34
    0.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1317
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method Covariance
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.30
    Confidence Interval (2-Sided) 95%
    0.92 to 1.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title 603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Number (95% Confidence Interval) [Proportion of subjects]
    0.40
    0.29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0113
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.60
    Confidence Interval (2-Sided) 95%
    1.11 to 2.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title 603A, Change in Seated Office Systolic Blood Pressure
    Description Placebo-adjusted change in seated office systolic blood pressure
    Time Frame Baseline (Day 1) to week 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (Standard Error) [mm Hg]
    -11.24
    (0.799)
    -6.61
    (0.787)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -4.63
    Confidence Interval (2-Sided) 95%
    -6.83 to -2.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title 603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (95% Confidence Interval) [Proportion of subjects]
    0.38
    0.25
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.86
    Confidence Interval (2-Sided) 95%
    1.32 to 2.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title 603A, Change in Mean Ambulatory Diastolic Blood Pressure
    Description Placebo-adjusted change in mean ambulatory diastolic blood pressure
    Time Frame Baseline (Day 1) to week 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (Standard Error) [mm Hg]
    -3.92
    (0.349)
    -3.08
    (0.337)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0863
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.83
    Confidence Interval (2-Sided) 95%
    -1.79 to 0.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title 603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (95% Confidence Interval) [Proportion of subjects]
    0.47
    0.37
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0232
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.48
    Confidence Interval (2-Sided) 95%
    1.06 to 2.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title 603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (95% Confidence Interval) [Proportion of subjects]
    0.88
    0.80
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0140
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.81
    Confidence Interval (2-Sided) 95%
    1.13 to 2.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title 603A, Change in Seated Office Diastolic Blood Pressure
    Description Placebo-adjusted change in seated office diastolic blood pressure
    Time Frame Baseline (Day 1) to week 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (Standard Error) [mm Hg]
    -4.44
    (0.504)
    -2.13
    (0.496)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0011
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.31
    Confidence Interval (2-Sided) 95%
    -3.70 to -0.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title 603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 334 339
    Least Squares Mean (95% Confidence Interval) [Proportion of subjects]
    0.65
    0.53
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0094
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.63
    Confidence Interval (2-Sided) 95%
    1.13 to 2.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Secondary Outcome
    Title 603B, Change in Seated Office Systolic Blood Pressure
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 281 281
    Least Squares Mean (Standard Error) [mm Hg]
    1.98
    (0.846)
    5.18
    (0.859)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0083
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -3.20
    Confidence Interval (2-Sided) 95%
    -5.57 to -0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Secondary Outcome
    Title 603B, Change in Mean Ambulatory Diastolic Blood Pressure
    Description Placebo-adjusted change in mean ambulatory diastolic blood pressure
    Time Frame Week 12 (cumulative week 24) to Week 24 (cumulative week 36)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 281 281
    Least Squares Mean (Standard Error) [mm Hg]
    0.10
    (0.369)
    0.94
    (0.368)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1085
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.84
    Confidence Interval (2-Sided) 95%
    -1.87 to 0.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title 603B, Change in Seated Office Diastolic Blood Pressure
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
    Measure Participants 281 281
    Least Squares Mean (Standard Error) [mm Hg]
    0.51
    (0.507)
    1.76
    (0.514)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0837
    Comments
    Method Covariance
    Comments Covariance model diabetes status, eGFR at screening, pre-treatment status, treatment, and baseline 24-hour mean SBP
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.25
    Confidence Interval (2-Sided) 95%
    -2.67 to 0.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Other Pre-specified Outcome
    Title Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Number of subjects with baseline and value after specified weeks of exposure to Bexagliflozin
    Arm/Group Title Effect on Mean Ambulatory SBP Effect on Mean Ambulatory DBP
    Arm/Group Description Effect on ABPM SBP after 12, 24, and 36 weeks of cumulative exposure to Bexagliflozin Effect on ABPM DBP after 12, 24, and 36 weeks of cumulative exposure to Bexagliflozin
    Measure Participants 649 649
    12 Weeks
    -7.595
    -3.269
    24 Weeks
    -9.262
    -4.044
    36 Weeks
    -12.454
    -5.566
    16. Other Pre-specified Outcome
    Title Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Number of subjects with baseline and value after specified weeks of exposure to Bexagliflozin
    Arm/Group Title Effect on Seated Office SBP Effect on Seated Office DBP
    Arm/Group Description Effect on seated office SBP after 6, 12, 18, 24, and 36 weeks of cumulative exposure to Bexagliflozin Effect on seated office DBP after 6, 12, 18, 24, and 36 weeks of cumulative exposure to Bexagliflozin
    Measure Participants 649 649
    6 Weeks
    -8.43
    (16.399)
    -4.50
    (9.534)
    12 Weeks
    -9.91
    (15.777)
    -4.10
    (9.716)
    18 Weeks
    -14.46
    (16.000)
    -5.87
    (9.282)
    24 Weeks
    -12.53
    (18.830)
    -4.92
    (10.910)
    36 Weeks
    -15.71
    (16.975)
    -6.47
    (9.933)

    Adverse Events

    Time Frame For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
    Adverse Event Reporting Description
    Arm/Group Title 603A: Bexagliflozin Tablets, 20 mg 603A: Placebo Tablets 603B: Bexagliflozin Tablets, 20 mg 603B: Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks. Each subject will receive placebo (inactive tablet) once daily for 12 weeks. 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. 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 tablets (inactive), 20 mg once daily for 12 weeks.
    All Cause Mortality
    603A: Bexagliflozin Tablets, 20 mg 603A: Placebo Tablets 603B: Bexagliflozin Tablets, 20 mg 603B: Placebo Tablets
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/334 (0%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Serious Adverse Events
    603A: Bexagliflozin Tablets, 20 mg 603A: Placebo Tablets 603B: Bexagliflozin Tablets, 20 mg 603B: Placebo Tablets
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/334 (3.3%) 10/339 (2.9%) 9/281 (3.2%) 6/281 (2.1%)
    Blood and lymphatic system disorders
    Anaemia 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Cardiac disorders
    Angina unstable 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Atrial flutter 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Coronary artery disease 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Myocardial infarction 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 1/281 (0.4%)
    Atrial fibrillation 0/334 (0%) 0/339 (0%) 2/281 (0.7%) 0/281 (0%)
    Eye disorders
    Diplopia 0/334 (0%) 0/339 (0%) 0/281 (0%) 1/281 (0.4%)
    Gastrointestinal disorders
    Enterocutaneous fistula 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Pancreatitis 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Crohn's disease 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Intestinal obstruction 0/334 (0%) 0/339 (0%) 0/281 (0%) 1/281 (0.4%)
    Large intestine polyp 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    General disorders
    Cyst 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Hepatobiliary disorders
    Bile duct stone 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Infections and infestations
    Abdominal abscess 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Arthritis infective 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Diverticulitis 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Pneumonia 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Necrotising fasciitis 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Injury, poisoning and procedural complications
    Ligament sprain 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Limb traumatic amputation 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Pelvic fracture 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Investigations
    Anticoagulation drug level below therapeutic 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Metabolism and nutrition disorders
    Hypoglycaemia 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Hypovolaemia 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 2/334 (0.6%) 0/339 (0%) 0/281 (0%) 1/281 (0.4%)
    Arthritis 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Spinal osteoarthritis 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Muscle rupture 0/334 (0%) 0/339 (0%) 0/281 (0%) 1/281 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of salivary gland 1/334 (0.3%) 0/339 (0%) 0/281 (0%) 0/281 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 1/281 (0.4%)
    Pulmonary embolism 1/334 (0.3%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Epistaxis 0/334 (0%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Vascular disorders
    Deep vein thrombosis 1/334 (0.3%) 0/339 (0%) 1/281 (0.4%) 0/281 (0%)
    Hypertension 0/334 (0%) 1/339 (0.3%) 0/281 (0%) 0/281 (0%)
    Other (Not Including Serious) Adverse Events
    603A: Bexagliflozin Tablets, 20 mg 603A: Placebo Tablets 603B: Bexagliflozin Tablets, 20 mg 603B: Placebo Tablets
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 94/334 (28.1%) 88/339 (26%) 32/281 (11.4%) 37/281 (13.2%)
    Gastrointestinal disorders
    Abdominal pain 2/334 (0.6%) 2 2/339 (0.6%) 2 2/281 (0.7%) 2 3/281 (1.1%) 3
    Constipation 6/334 (1.8%) 7 3/339 (0.9%) 3 1/281 (0.4%) 1 1/281 (0.4%) 1
    Diarrhoea 4/334 (1.2%) 4 5/339 (1.5%) 5 1/281 (0.4%) 1 2/281 (0.7%) 2
    Dry mouth 4/334 (1.2%) 4 2/339 (0.6%) 2 0/281 (0%) 0 1/281 (0.4%) 1
    Nausea 7/334 (2.1%) 7 5/339 (1.5%) 5 1/281 (0.4%) 1 3/281 (1.1%) 3
    Vomiting 3/334 (0.9%) 3 6/339 (1.8%) 6 1/281 (0.4%) 1 2/281 (0.7%) 2
    General disorders
    Oedema peripheral 3/334 (0.9%) 3 7/339 (2.1%) 7 0/281 (0%) 0 1/281 (0.4%) 1
    Infections and infestations
    Bronchitis 2/334 (0.6%) 2 5/339 (1.5%) 5 1/281 (0.4%) 1 3/281 (1.1%) 3
    Gastroenteritis 3/334 (0.9%) 3 1/339 (0.3%) 1 1/281 (0.4%) 1 3/281 (1.1%) 3
    Genital infection fungal 4/334 (1.2%) 8 0/339 (0%) 0 2/281 (0.7%) 2 0/281 (0%) 0
    Influenza 5/334 (1.5%) 5 3/339 (0.9%) 3 0/281 (0%) 0 0/281 (0%) 0
    Nasopharyngitis 12/334 (3.6%) 12 11/339 (3.2%) 11 4/281 (1.4%) 4 2/281 (0.7%) 2
    Upper respiratory tract infection 5/334 (1.5%) 5 10/339 (2.9%) 11 1/281 (0.4%) 1 3/281 (1.1%) 3
    Urinary tract infection 7/334 (2.1%) 7 7/339 (2.1%) 7 6/281 (2.1%) 6 6/281 (2.1%) 7
    Injury, poisoning and procedural complications
    Ligament sprain 6/334 (1.8%) 6 0/339 (0%) 0 1/281 (0.4%) 1 2/281 (0.7%) 2
    Metabolism and nutrition disorders
    Polydipsia 3/334 (0.9%) 3 5/339 (1.5%) 5 1/281 (0.4%) 1 2/281 (0.7%) 2
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/334 (0.6%) 2 5/339 (1.5%) 5 1/281 (0.4%) 1 3/281 (1.1%) 3
    Back pain 5/334 (1.5%) 5 5/339 (1.5%) 5 1/281 (0.4%) 2 1/281 (0.4%) 1
    Musculoskeletal pain 1/334 (0.3%) 1 1/339 (0.3%) 1 3/281 (1.1%) 4 0/281 (0%) 0
    Pain in extremity 2/334 (0.6%) 2 2/339 (0.6%) 2 3/281 (1.1%) 3 2/281 (0.7%) 2
    Nervous system disorders
    Dizziness 7/334 (2.1%) 7 1/339 (0.3%) 1 3/281 (1.1%) 3 1/281 (0.4%) 1
    Headache 4/334 (1.2%) 4 7/339 (2.1%) 7 1/281 (0.4%) 1 2/281 (0.7%) 2
    Renal and urinary disorders
    Pollakiuria 13/334 (3.9%) 13 4/339 (1.2%) 4 0/281 (0%) 0 0/281 (0%) 0
    Polyuria 4/334 (1.2%) 4 9/339 (2.7%) 9 2/281 (0.7%) 2 1/281 (0.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 4/334 (1.2%) 4 4/339 (1.2%) 4 2/281 (0.7%) 2 1/281 (0.4%) 1
    Skin and subcutaneous tissue disorders
    Rash 2/334 (0.6%) 2 3/339 (0.9%) 3 1/281 (0.4%) 1 3/281 (1.1%) 3
    Vascular disorders
    Hypertension 1/334 (0.3%) 1 6/339 (1.8%) 6 2/281 (0.7%) 2 2/281 (0.7%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Investigator has no right to publish the study results.

    Results Point of Contact

    Name/Title Albert Collinson
    Organization Theracos Sub, LLC
    Phone (508) 688-4221
    Email acollinson@theracos.com
    Responsible Party:
    Theracos
    ClinicalTrials.gov Identifier:
    NCT03514641
    Other Study ID Numbers:
    • THR-1442-C-603
    First Posted:
    May 2, 2018
    Last Update Posted:
    Sep 21, 2021
    Last Verified:
    Aug 1, 2021