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

Sponsor
Theracos (Industry)
Overall Status
Completed
CT.gov ID
NCT02390050
Collaborator
(none)
292
Enrollment
50
Locations
4
Arms
12.7
Actual Duration (Months)
5.8
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to investigate the effect of bexagliflozin in lowering hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Bexagliflozin is an orally administered drug for the treatment of T2DM and is classified as a Sodium Glucose co-Transporter 2 (SGLT2) Inhibitor. This study was to enroll both treatment naive and those subjects previously treated with one oral hypoglycemic agent (OHA). Approximately 320 subjects eligible for randomization was to receive bexagliflozin tablets, 5, 10, 20 mg or placebo, once daily for 12 weeks in an outpatient setting.

Condition or Disease Intervention/Treatment Phase
  • Drug: Bexagliflozin tablets
  • Drug: Bexagliflozin tablets, placebo
 Phase 2

Detailed Description

The study was a phase 2b multicenter, double-blind, placebo-controlled parallel group study to assess the effect of once daily bexagliflozin tablets on HbA1c in either treatment-naïve T2DM subjects or in subjects who were treated with one oral anti-diabetic agent. Treatment naïve subjects were eligible if their HbA1c values were between 7% and 8.5% at the screening visit while subjects who were treated with one oral hypoglycemic agent (OHA) were eligible if their HbA1c value was between 6.5% and 8.5% at screening and underwent a 6 or 10 week washout period. In addition, all eligible subjects underwent a two week placebo run-in period and those who showed good compliance in taking study medication (i.e., missed no more than one dose during the run-in period) during this period and whose HbA1c values were between 7 and 8.5% at the end of the run-in period were eligible for randomization.

Study Design

Study Type:
Interventional
Actual Enrollment :
292 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2b, Multi-center, Double-blind, Placebo-controlled, Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets on HbA1c in Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date :
May 12, 2015
Actual Primary Completion Date :
Jun 3, 2016
Actual Study Completion Date :
Jun 3, 2016

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Bexagliflozin tablets, 5 mg

Bexagliflozin tablets, 5 mg, once daily by mouth before breakfast

Drug: Bexagliflozin tablets
Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Other Names:
  • Code name: EGT0001442

    		•
    Active Comparator: Bexagliflozin tablets, 10 mg

    Bexagliflozin tablets, 10 mg, once daily by mouth before breakfast

    Drug: Bexagliflozin tablets
    Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Other Names:
  • Code name: EGT0001442

    		•
    Active Comparator: Bexagliflozin tablets, 20 mg

    Bexagliflozin tablets, 20 mg, once daily by mouth before breakfast

    Drug: Bexagliflozin tablets
    Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Other Names:
  • Code name: EGT0001442

    		•
    Placebo Comparator: Bexagliflozin tablets, placebo

    Bexagliflozin tablets, placebo, once daily by mouth before breakfast

    Drug: Bexagliflozin tablets, placebo
    Bexagliflozin tablets, placebo, are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.

    Outcome Measures

    Primary Outcome Measures

    1. Change in HbA1c After 12 Weeks of Treatment [12 weeks]

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

    Secondary Outcome Measures

    1. Proportion of Subjects With HbA1c < 7% [Baseline to up to 12 weeks]

      To assess the efficacy of bexagliflozin based on the proportion of subjects who reach the American Diabetes Associate (ADA) and the Japan Diabetes Society target HbA1c of <7%.

    2. Change in Body Weight Over Time [Baseline to Week 2, Week 6 and Week 12]

      The body weight was analyzed on the full analysis set using the MMRM ANCOVA model used for the primary efficacy analysis.

    3. Change in Fasting Plasma Glucose (FPG) Over Time [Baseline to Week 2, Week 6 and Week 12]

      The fasting plasma glucose (FPG) was analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.

    4. Change in Systolic and Diastolic Blood Pressure Over Time [Baseline to Week 2, Week 6 and Week 12]

      The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.

    5. Change in HbA1c Over Time [Baseline to Week 2, Week 6 and Week 12]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    The following subjects were eligible for randomization:

    1. men or women ≥ 20 years of age at screening. Women of childbearing potential must test negative by urine pregnancy test.

    2. were treatment naïve or taking one oral anti-diabetic medication in combination with diet and exercise

    3. were diagnosed with T2DM with HbA1c levels at screening between 7.0% and 8.5% (inclusive) if treatment naïve or with HbA1c levels between 6.5 and 8.5% (inclusive) if on one oral anti-diabetic medication

    4. had a body mass index (BMI) ≤ 40 kg/m2

    5. were taking stable doses of medication for hypertension or hyperlipidemia that has not changed for at least 30 days prior to screening (if applicable)

    6. were able to comprehend the study participation requirements and willing to provide written informed consent in accordance with institutional and regulatory guidelines

    7. were able to maintain adequate glycemic control at the run-in visit (for subjects who complete the washout)

    8. had an HbA1c between 7.0 and 8.5% (inclusive) prior to randomization (day -3 to -5)

    9. were capable of adhering to the investigational product administration requirements as evidenced by omission of no more than one dose of run-in medication

    Subjects who exhibited any of the following characteristics were to be ineligible for randomization:

    1. Diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young

    2. Used parenteral therapy for treatment of diabetes

    3. Pregnancy or current breastfeeding status

    4. Hemoglobinopathy or carrier status for hemoglobin alleles that affect HbA1c measurement

    5. Genitourinary tract infection within 6 weeks of screening or history of ≥3 genitourinary infections requiring treatment within 6 months of screening

    6. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at screening.

    7. Uncontrolled hypertension at screening

    8. A positive result on hepatitis B surface antigen, hepatitis C, or positive result from screen for drugs of abuse

    9. History of human immunodeficiency virus infection

    10. Life expectancy < 2 years

    11. History of New York Heart Association Class 4 heart failure within 3 months of screening

    12. History of myocardial infarction, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening

    13. History of treatment with an investigational drug within 30 days or within 7 half lives of the investigational drug, whichever is longer

    14. Previous treatment with bexagliflozin

    15. Had taken or within 6 months of taking any Sodium Glucose Transporter 2 (SGLT2) inhibitors prior to screening

    16. Participation of another interventional trial

    17. Not able to comply with the study scheduled visits

    18. Affected by any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the investigator, would jeopardize the subject's appropriate participation in this study.

    19. Liver function tests resulting in Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN, with the exception of isolated Gilbert's syndrome ,at screening

    20. Exhibited fasting plasma glucose ≥ 250 mg/dL (13.9 mmol/L) on two or more consecutive days prior to randomization or exhibited severe clinical signs or symptoms of hyperglycemia during the washout or run-in periods, including weight loss, blurred vision, increased thirst, or increased urination, or fatigue

    21. Fasting Plasma Glucose ≥ 250 mg/dL at randomization

    22. Prior renal transplantation or evidence of nephrotic syndrome, defined as a urine albumin-to-creatinine ratio (UACR) > 2000 mg/g at screening

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Medical Research Institute LLC Peoria Arizona United States 85381
    2 Advanced Arizona Clinical Research Tucson Arizona United States 85712
    3 Hope Clinical Research, LLC Canoga Park California United States 91303
    4 Catalina Research Institute Chino California United States 91710
    5 National Research Institute Huntington Park California United States 90255
    6 Long Beach Clinical Trials Long Beach California United States 90806
    7 Synergy San Diego National City California United States 91950
    8 Northern California Research Sacramento California United States 95821
    9 Artemis Institute for Clinical Research, LLC San Diego California United States 92103
    10 Infosphere Clinical Research, Inc West Hills California United States 91307
    11 M&O Clinical Research LLC Fort Lauderdale Florida United States 33316
    12 AGA Clinical Trials Hialeah Florida United States 33012
    13 Compass Research North Leesburg Florida United States 34748
    14 Sweet Hope Research Specialty, Inc Miami Lakes Florida United States 33016
    15 Sunshine Research Center Opa-locka Florida United States 33054
    16 Compass Research LLC Orlando Florida United States 32806
    17 Progressive Medical Research Port Orange Florida United States 32127
    18 PICR Clinic Atlanta Georgia United States 30338
    19 Sundance Clinical Research Saint Louis Missouri United States 63141
    20 Premier Research Ltd Trenton New Jersey United States 08611
    21 Regional Clinical Research, Inc Endwell New York United States 13760
    22 Calabash Medical Center Calabash North Carolina United States 28467
    23 Diabetes & Endocrinology Consultants PC Morehead City North Carolina United States 28557
    24 PMG Research of Salisbury Salisbury North Carolina United States 28144
    25 CTI Research Cincinnati Ohio United States 45255
    26 Summit Research Group, LLC Stow Ohio United States 44224
    27 Columbia Research Group, Inc. Portland Oregon United States 97239
    28 Detweiler Family Medicine and Associate, P.C. Lansdale Pennsylvania United States 19446
    29 North Myrtle Beach Family Practice Myrtle Beach South Carolina United States 29582
    30 Global Medical Research DeSoto Texas United States 75115
    31 Rockwood Medical Clinic Fort Worth Texas United States 76164
    32 Wasatch Clinical Research Salt Lake City Utah United States 84107
    33 Medical Corporation Hitomi-kai Motomachi Takatsuka Naika Clinic Yokohama Naka-ku Kanagawa Japan 231-0023
    34 Medical Corporation Hayashi katagihara Clinic Nishikyo-ku Kyoto Japan 615-8125
    35 Medical Corporation KEISEIKAI Kajiyama clinic Ukyou-ku Kyoto Japan 615-0035
    36 Ikeoka Medical Corp. Ikeoka Clinic Joto-ku Osaka Japan 536-0008
    37 Miyauchi Medical Center Takatsuki-shi Osaka Japan 569-1123
    38 Medical Corporation Senrichuo Ekimae Clinic Toyonaka-shi Osaka Japan 560-0082
    39 Medical Corporation Segawa Hospital Hikigun Ogawamachi Saitama Japan 355-0328
    40 Medical Corporation Yukeikai Asano Clinic Kawagoe-shi Saitama Japan 350-0851
    41 Medical Corporation Ishii Internal Medicine Clinic Kawaguchi Saitama Japan 333-0844
    42 Medical Corporation Fusanokai Shimizu Clinic Fusa Saitama-shi Saitama Japan 336-0963
    43 Medical Corp. SEIKOUKAI New Medical Research System Clinic Hachioji-shi Tokyo Japan 192-0046
    44 Medical Corporation Jototowakai Shinkoiwa ekimae sogo Clinic Katsushika-ku Tokyo Japan 124-0024
    45 Medical Corporation IHL Pedi Shiodome Medical Clinic Minato-ku Tokyo Japan 105-7390
    46 Medical Corporation IHL Shinagawa East One Medical Clinic Minato-ku Tokyo Japan 108-0075
    47 Kenkokan Suzuki Clinic Ota-ku Tokyo Japan 143-0015
    48 Medical Corporation Souyu-kai Hirahata Clinic Shibuya-ku Tokyo Japan 150-0002
    49 Medical Corporation Yuhokai Miho-Clinic Shinagawa-ku Tokyo Japan 141-0032
    50 Ikebukuro Metropolitan Clinic Toshima-ku Tokyo Japan 171-0021

    Sponsors and Collaborators

    • Theracos

    Investigators

    • Study Director: J Paul Lock, M.D., Theracos

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Theracos
    ClinicalTrials.gov Identifier:
    NCT02390050
    Other Study ID Numbers:
    • THR-1442-C-449
    First Posted:
    Mar 17, 2015
    Last Update Posted:
    Jun 29, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Bexagliflozin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Period Title: Overall Study
    STARTED 72 72 72 76
    COMPLETED 65 67 68 69
    NOT COMPLETED 7 5 4 7

    Baseline Characteristics

    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg Total
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Total of all reporting groups
    Overall Participants 72 72 72 76 292
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.8
    (10.42)
    59.0
    (10.22)
    59.4
    (8.99)
    59.5
    (10.81)
    59.2
    (10.99)
    Sex: Female, Male (Count of Participants)
    Female
    30
    41.7%
    25
    34.7%
    31
    43.1%
    26
    34.2%
    112
    38.4%
    Male
    42
    58.3%
    47
    65.3%
    41
    56.9%
    50
    65.8%
    180
    61.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    14
    19.4%
    17
    23.6%
    12
    16.7%
    15
    19.7%
    58
    19.9%
    Not Hispanic or Latino
    57
    79.2%
    55
    76.4%
    58
    80.6%
    61
    80.3%
    231
    79.1%
    Unknown or Not Reported
    1
    1.4%
    0
    0%
    2
    2.8%
    0
    0%
    3
    1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    1.4%
    0
    0%
    0
    0%
    1
    0.3%
    Asian
    37
    51.4%
    38
    52.8%
    39
    54.2%
    41
    53.9%
    155
    53.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    8
    11.1%
    5
    6.9%
    9
    12.5%
    8
    10.5%
    30
    10.3%
    White
    27
    37.5%
    27
    37.5%
    23
    31.9%
    26
    34.2%
    103
    35.3%
    More than one race
    0
    0%
    1
    1.4%
    0
    0%
    1
    1.3%
    2
    0.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    1.4%
    0
    0%
    1
    0.3%
    Region of Enrollment (participants) [Number]
    United States
    36
    50%
    36
    50%
    33
    45.8%
    37
    48.7%
    142
    48.6%
    Japan
    36
    50%
    36
    50%
    39
    54.2%
    39
    51.3%
    150
    51.4%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    165.6
    (10.63)
    165.7
    (9.25)
    165.8
    (9.03)
    166.0
    (10.33)
    165.8
    (9.79)
    Body Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    78.72
    (19.747)
    80.52
    (18.977)
    78.39
    (17.589)
    78.84
    (16.740)
    79.11
    (18.204)
    BMI (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    28.54
    (5.535)
    29.10
    (5.211)
    28.35
    (4.978)
    28.49
    (5.010)
    28.62
    (5.167)

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    Subjects who were randomized, took at least one dose of double-blind study medication, and had at least one post-randomization HbA1c measurement were included in the full analysis dataset (FAS). TheHbA1c change from baseline through 12 weeks, and the primary analysis is based on the available data and data obtained after rescue will be excluded and considered missing.
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Measure Participants 64 65 68 68
    Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]
    0.24
    (0.08)
    -0.31
    (0.08)
    -0.44
    (0.08)
    -0.56
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.55
    Confidence Interval (2-Sided) 95%
    -0.76 to -0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.68
    Confidence Interval (2-Sided) 95%
    -0.89 to -0.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.80
    Confidence Interval (2-Sided) 95%
    -1.01 to -0.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Proportion of Subjects With HbA1c < 7%
    Description To assess the efficacy of bexagliflozin based on the proportion of subjects who reach the American Diabetes Associate (ADA) and the Japan Diabetes Society target HbA1c of <7%.
    Time Frame Baseline to up to 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects with at least one post-baseline HbA1c value <7% met this endpoint. HbA1c values obtained after start of rescue medication were excluded from this analysis. The number and percentage of subjects with at least one HbA1c value <7% were summarized by treatment group for the FAS.
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Measure Participants 72 71 72 75
    Count of Participants [Participants]
    11
    15.3%
    15
    20.8%
    16
    22.2%
    27
    35.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Odds ratio of having at least 1 post-baseline HbA1c value <7% in the 5 mg bexagliflozin group was compared to placebo group.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1308
    Comments
    Method Regression, Logistic
    Comments Treatment, country, baseline HbA1c and prior anti-diabetic treatment status as predictor variables and a dependable variable of 1 (<7%) or 0 (>7%).
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.1
    Confidence Interval (2-Sided) 95%
    0.8 to 5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Odds ratio of having at least 1 post-baseline HbA1c value <7% in the 10 mg bexagliflozin group was compared to placebo group.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1294
    Comments
    Method Regression, Logistic
    Comments Treatment, country, baseline HbA1c and prior anti-diabetic treatment status as predictor variables and a dependable variable of 1 (<7%) or 0 (>7%).
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.0
    Confidence Interval (2-Sided) 95%
    0.8 to 5.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Odds ratio of having at least 1 post-baseline HbA1c value <7% in the 20 mg bexagliflozin group was compared to placebo group.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0015
    Comments
    Method Regression, Logistic
    Comments Treatment, country, baseline HbA1c and prior anti-diabetic treatment status as predictor variables and a dependable variable of 1 (<7%) or 0 (>7%).
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.2
    Confidence Interval (2-Sided) 95%
    1.7 to 10.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change in Body Weight Over Time
    Description The body weight was analyzed on the full analysis set using the MMRM ANCOVA model used for the primary efficacy analysis.
    Time Frame Baseline to Week 2, Week 6 and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only subject with a value at the specified time is included
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Measure Participants 72 71 72 75
    Week 2
    0.00
    (0.15)
    -0.74
    (0.16)
    -0.76
    (0.15)
    -0.99
    (0.15)
    Week 6
    0.02
    (0.19)
    -1.00
    (0.19)
    -1.42
    (0.19)
    -1.49
    (0.19)
    Week 12
    -0.14
    (0.25)
    -1.58
    (0.25)
    -1.72
    (0.25)
    -1.89
    (0.25)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 2: Difference in LS mean change in body weight from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.74
    Confidence Interval (2-Sided) 95%
    -1.13 to -0.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 2: Difference in LS mean change in body weight from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.76
    Confidence Interval (2-Sided) 95%
    -1.15 to -0.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 2: Difference in LS mean change in body weight from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.99
    Confidence Interval (2-Sided) 95%
    -1.38 to -0.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 6: Difference in LS mean change in body weight from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -1.53 to -0.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 6: Difference in LS mean change in body weight from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.45
    Confidence Interval (2-Sided) 95%
    -1.95 to -0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 6: Difference in LS mean change in body weight from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.51
    Confidence Interval (2-Sided) 95%
    -2.01 to -1.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 12: Difference in LS mean change in body weight from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline weight as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.44
    Confidence Interval (2-Sided) 95%
    -2.12 to -0.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 12: Difference in LS mean change in body weight from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline weight as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.59
    Confidence Interval (2-Sided) 95%
    -2.26 to -0.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 12: Difference in LS mean change in body weight from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline weight as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.75
    Confidence Interval (2-Sided) 95%
    -2.43 to -1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Change in Fasting Plasma Glucose (FPG) Over Time
    Description The fasting plasma glucose (FPG) was analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.
    Time Frame Baseline to Week 2, Week 6 and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only subject with a value at the specified time is included
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Measure Participants 72 71 72 75
    Week 2
    -0.07
    (0.16)
    -0.55
    (0.16)
    -0.97
    (0.16)
    -1.11
    (0.15)
    Week 6
    0.11
    (0.17)
    -0.82
    (0.17)
    -1.06
    (0.17)
    -0.99
    (0.17)
    Week 12
    -0.11
    (0.17)
    -0.96
    (0.17)
    -1.16
    (0.17)
    -1.18
    (0.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 2: Difference in LS mean change in FPG from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.48
    Confidence Interval (2-Sided) 95%
    -0.90 to -0.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 2: Difference in LS mean change in FPG from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.90
    Confidence Interval (2-Sided) 95%
    -1.31 to -0.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 2: Difference in LS mean change in FPG from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.04
    Confidence Interval (2-Sided) 95%
    -1.45 to -0.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 6: Difference in LS mean change in FPG from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.93
    Confidence Interval (2-Sided) 95%
    -1.39 to -0.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 6: Difference in LS mean change in FPG from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.17
    Confidence Interval (2-Sided) 95%
    -1.62 to -0.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 6: Difference in LS mean change in FPG from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.10
    Confidence Interval (2-Sided) 95%
    -1.55 to -0.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 12: Difference in LS mean change in FPG from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0002
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline FPG as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.85
    Confidence Interval (2-Sided) 95%
    -1.29 to -0.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 12: Difference in LS mean change in FPG from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline FPG as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.05
    Confidence Interval (2-Sided) 95%
    -1.49 to -0.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 12: Difference in LS mean change in FPG from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline FPG as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.07
    Confidence Interval (2-Sided) 95%
    -1.52 to -0.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change in Systolic and Diastolic Blood Pressure Over Time
    Description The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.
    Time Frame Baseline to Week 2, Week 6 and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only subject with a value at the specified time is included
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Measure Participants 72 71 72 75
    Week 2 SBP
    -0.14
    (1.42)
    -0.33
    (1.43)
    -2.55
    (1.42)
    -4.39
    (1.38)
    Week 2 DBP
    0.15
    (0.89)
    -0.03
    (0.89)
    -1.59
    (0.88)
    -2.00
    (0.86)
    Week 6 SBP
    -0.57
    (1.44)
    -1.40
    (1.45)
    -3.96
    (1.44)
    -3.07
    (1.39)
    Week 6 DBP
    -0.52
    (0.92)
    -0.27
    (0.93)
    -1.54
    (0.92)
    -0.36
    (0.89)
    Week 12 SBP
    1.10
    (1.56)
    -1.06
    (1.57)
    -3.30
    (1.55)
    -2.73
    (1.55)
    Week 12 DBP
    0.81
    (0.95)
    -1.43
    (0.95)
    -0.66
    (0.94)
    -1.23
    (0.94)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 2: Difference in LS mean change in SBP from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -3.90 to 3.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 2: Difference in LS mean change in SBP from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -2.41
    Confidence Interval (2-Sided) 95%
    -6.09 to 1.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 2: Difference in LS mean change in SBP from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -4.25
    Confidence Interval (2-Sided) 95%
    -7.93 to -0.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 2: Difference in LS mean change in DBP from baseline to week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -2.50 to 2.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 2: Difference in LS mean change in DBP from baseline to week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.74
    Confidence Interval (2-Sided) 95%
    -4.03 to 0.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 2: Difference in LS mean change in DBP from baseline to week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -2.15
    Confidence Interval (2-Sided) 95%
    -4.45 to 0.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 6: Difference in LS mean change in SBP from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.84
    Confidence Interval (2-Sided) 95%
    -4.57 to 2.90
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 6: Difference in LS mean change in SBP from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -3.39
    Confidence Interval (2-Sided) 95%
    -7.12 to 0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 6: Difference in LS mean change in SBP from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -2.51
    Confidence Interval (2-Sided) 95%
    -6.21 to 1.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 6: Difference in LS mean change in DBP from baseline to week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value 0.25
    Confidence Interval (2-Sided) 95%
    -2.15 to 2.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 6: Difference in LS mean change in DBP from baseline to week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -3.42 to 1.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 6: Difference in LS mean change in DBP from baseline to week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.84
    Confidence Interval (2-Sided) 95%
    -3.22 to 1.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 12: Difference in LS mean change in SBP from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -2.16
    Confidence Interval (2-Sided) 95%
    -6.26 to 1.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 12: Difference in LS mean change in SBP from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0343
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -4.41
    Confidence Interval (2-Sided) 95%
    -8.49 to -0.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 12: Difference in LS mean change in SBP from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0679
    Comments
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -3.83
    Confidence Interval (2-Sided) 95%
    -7.95 to 0.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 12: Difference in LS mean change in DBP from baseline to week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0776
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -2.24
    Confidence Interval (2-Sided) 95%
    -4.73 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 12: Difference in LS mean change in DBP from baseline to week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2415
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -1.47
    Confidence Interval (2-Sided) 95%
    -3.95 to 1.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 12: Difference in LS mean change in DBP from baseline to week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1086
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline SBP as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -2.04
    Confidence Interval (2-Sided) 95%
    -4.54 to 0.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Change in HbA1c Over Time
    Description The least square mean (LSM) change from baseline to Week 2, Week 6 and Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes. The LSM change was calculated by excluding HbA1c data obtained after rescue medication.
    Time Frame Baseline to Week 2, Week 6 and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only subject with a value at the specified time is included
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    Measure Participants 72 71 72 75
    Week 2
    -0.00
    (0.04)
    -0.09
    (0.04)
    -0.13
    (0.04)
    -0.13
    (0.04)
    Week 6
    0.13
    (0.06)
    -0.32
    (0.06)
    -0.36
    (0.06)
    -0.40
    (0.06)
    Week 12
    0.24
    (0.08)
    -0.31
    (0.08)
    -0.44
    (0.08)
    -0.56
    (0.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 2: Difference in LS Mean change in HbA1c (%) from baseline to Week 2 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.09
    Confidence Interval (2-Sided) 95%
    -0.20 to 0.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 2: Difference in LS Mean change in HbA1c (%) from baseline to Week 2 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.24 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 2: Difference in LS Mean change in HbA1c (%) from baseline to Week 2 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.13
    Confidence Interval (2-Sided) 95%
    -0.24 to -0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 6: Difference in LS Mean change in HbA1c (%) from baseline to Week 6 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.45
    Confidence Interval (2-Sided) 95%
    -0.62 to -0.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 6: Difference in LS Mean change in HbA1c (%) from baseline to Week 6 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.49
    Confidence Interval (2-Sided) 95%
    -0.66 to -0.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 6: Difference in LS Mean change in HbA1c (%) from baseline to Week 6 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.53
    Confidence Interval (2-Sided) 95%
    -0.70 to -0.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 5 mg
    Comments Week 12: Difference in LS Mean change in HbA1c (%) from baseline to Week 12 was obtained by comparing Bexagliflozin 5 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.55
    Confidence Interval (2-Sided) 95%
    -0.76 to -0.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 10 mg
    Comments Week 12: Difference in LS Mean change in HbA1c (%) from baseline to Week 12 was obtained by comparing Bexagliflozin 10 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.68
    Confidence Interval (2-Sided) 95%
    -0.89 to -0.47
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, Bexagliflozin 20 mg
    Comments Week 12: Difference in LS Mean change in HbA1c (%) from baseline to Week 12 was obtained by comparing Bexagliflozin 20 mg group and Placebo group
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments P-value from Type III F-test
    Method ANCOVA
    Comments Study center, treatment, visit and a treatment-by-visit interaction as fixed effects; prior anti-diabetic treatment and baseline HbA1c as covariates
    Method of Estimation Estimation Parameter Difference of LS Means
    Estimated Value -0.80
    Confidence Interval (2-Sided) 95%
    -1.01 to -0.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
    Adverse Event Reporting Description
    Arm/Group Title Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Arm/Group Description Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans. Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
    All Cause Mortality
    Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/72 (0%) 0/72 (0%) 0/72 (0%) 0/76 (0%)
    Serious Adverse Events
    Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/72 (0%) 0/72 (0%) 3/72 (4.2%) 2/76 (2.6%)
    Cardiac disorders
    Acute myocardial infarction 0/72 (0%) 0/72 (0%) 1/72 (1.4%) 0/76 (0%)
    Hepatobiliary disorders
    Bile duct stone 0/72 (0%) 0/72 (0%) 1/72 (1.4%) 0/76 (0%)
    Infections and infestations
    Urinary Tract Infection 0/72 (0%) 0/72 (0%) 0/72 (0%) 1/76 (1.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant 0/72 (0%) 0/72 (0%) 1/72 (1.4%) 0/76 (0%)
    Gastroesophageal cancer 0/72 (0%) 0/72 (0%) 0/72 (0%) 1/76 (1.3%)
    Other (Not Including Serious) Adverse Events
    Placebo Bexagliflozin 5 mg Bexagliflozin 10 mg Bexagliflozin 20 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/72 (16.7%) 15/72 (20.8%) 18/72 (25%) 17/76 (22.4%)
    Eye disorders
    Vision blurred 0/72 (0%) 2/72 (2.8%) 0/72 (0%) 0/76 (0%)
    Gastrointestinal disorders
    Nausea 2/72 (2.8%) 0/72 (0%) 0/72 (0%) 0/76 (0%)
    Diarrhea 2/72 (2.8%) 2/72 (2.8%) 1/72 (1.4%) 0/76 (0%)
    General disorders
    Thirst 0/72 (0%) 0/72 (0%) 0/72 (0%) 2/76 (2.6%)
    Infections and infestations
    Nasopharyngitis 3/72 (4.2%) 5/72 (6.9%) 4/72 (5.6%) 3/76 (3.9%)
    Pharyngitis 0/72 (0%) 2/72 (2.8%) 3/72 (4.2%) 0/76 (0%)
    Urinary tract infection 1/72 (1.4%) 2/72 (2.8%) 1/72 (1.4%) 1/76 (1.3%)
    Viral upper respiratory tract infection 0/72 (0%) 0/72 (0%) 2/72 (2.8%) 0/76 (0%)
    Upper respiratory tract infection 2/72 (2.8%) 0/72 (0%) 1/72 (1.4%) 0/76 (0%)
    Metabolism and nutrition disorders
    Hypoglycemia 1/72 (1.4%) 0/72 (0%) 0/72 (0%) 4/76 (5.3%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/72 (1.4%) 0/72 (0%) 2/72 (2.8%) 0/76 (0%)
    Muscle spasms 2/72 (2.8%) 1/72 (1.4%) 0/72 (0%) 1/76 (1.3%)
    Arthralgia 0/72 (0%) 1/72 (1.4%) 2/72 (2.8%) 1/76 (1.3%)
    Nervous system disorders
    Dizziness 1/72 (1.4%) 2/72 (2.8%) 0/72 (0%) 0/76 (0%)
    Headache 2/72 (2.8%) 2/72 (2.8%) 2/72 (2.8%) 2/76 (2.6%)
    Renal and urinary disorders
    Dysuria 1/72 (1.4%) 0/72 (0%) 0/72 (0%) 3/76 (3.9%)
    Polyuria 0/72 (0%) 0/72 (0%) 0/72 (0%) 3/76 (3.9%)
    Pollakiuria 0/72 (0%) 2/72 (2.8%) 2/72 (2.8%) 2/76 (2.6%)
    Reproductive system and breast disorders
    Balanoposthitis 0/72 (0%) 0/72 (0%) 0/72 (0%) 2/76 (2.6%)
    Skin and subcutaneous tissue disorders
    Dermatitis 0/72 (0%) 0/72 (0%) 0/72 (0%) 2/76 (2.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Investigator has no publication right.

    Results Point of Contact

    Name/Title Albert Collinson
    Organization Theracos Sub, LLC
    Phone (508) 630-2129
    Email acollinson@theracos.com
    Responsible Party:
    Theracos
    ClinicalTrials.gov Identifier:
    NCT02390050
    Other Study ID Numbers:
    • THR-1442-C-449
    First Posted:
    Mar 17, 2015
    Last Update Posted:
    Jun 29, 2021
    Last Verified:
    Jun 1, 2021