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Safety and Efficacy of Bexagliflozin as Monotherapy in Patients With Type 2 Diabetes

Sponsor
Theracos (Industry)
Overall Status
Completed
CT.gov ID
NCT02715258
Collaborator
(none)
210
Enrollment
23
Locations
2
Arms
13
Actual Duration (Months)
9.1
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect of bexagliflozin in lowering hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This was a phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of once daily oral administration of bexagliflozin tablets, 20 mg or placebo tablets, in male and female subjects with T2DM who were treatment-naïve or previously treated with 1 oral hypoglycemic agent (OHA).

Prospective subjects being treated with one OHA were eligible if they had an HbA1c between 6.5% and 10.0% and were willing to complete a 6-week washout. Individuals taking thiazolidinediones were not eligible for the study. All eligible subjects were to start a 2-week placebo run-in period. Subjects who missed no more than 1 dose of the run-in medication, had fasting blood glucose values ≥ 250 mg/dL on no more than two consecutive days, and had an HbA1c level between 7.0% and 10.5% and a fasting glucose level < 250 mg/dL after the run-in period were eligible for randomization.

Two hundred and ten (210) subjects were planned to be randomly assigned to receive oral bexagliflozin tablets, 20 mg or placebo, in a 2:1 ratio once daily for 24 weeks. Subjects with uncontrolled hyperglycemia based on blood glucose levels could receive additional approved anti-diabetic medications. Treatment group assignment at the start of the treatment period was stratified by baseline HbA1c level and background anti-diabetes treatment status (treatment naïve or not).

Each subject was contacted by telephone at week 2 and was instructed to return to the clinic at weeks 6, 12, 18, and 24 for efficacy assessment and safety monitoring. Subjects returned to the clinic for a follow-up visit at week 26 or 2 weeks after the last dose of investigational product if the subject terminated prior to week 24.

Study Design

Study Type:
Interventional
Actual Enrollment :
210 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Compare the Efficacy and Safety of Bexagliflozin to Placebo in Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Actual Study Start Date :
Mar 1, 2016
Actual Primary Completion Date :
Apr 1, 2017
Actual Study Completion Date :
Apr 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Bexagliflozin tablets, 20 mg

Each subject will self-administer bexagliflozin tablets once daily for 24 weeks.

Drug: Bexagliflozin
tablets containing 20 mg bexagliflozin
Other Names:
  • EGT0001442

    		•
    Placebo Comparator: Placebo tablets

    Each subject will self-administer placebo (inactive tablet) once daily for 24 weeks.

    Drug: Placebo
    tablets matching the appearance of bexagliflozin tablets

    Outcome Measures

    Primary Outcome Measures

    1. Change in HbA1c From Baseline at Week 24 [24 weeks]

      Glycated hemoglobin A1c (%) was measured using an HPLC method in the laboratories that had completed NGSP Level I laboratory certification and were traceable to the Diabetes Control and Complications Trial (DCCT) reference method.

    Secondary Outcome Measures

    1. Change in Systolic Blood Pressure (SBP) From Baseline at Week 24 [24 weeks]

      Blood pressure (BP) measurements are obtained using a calibrated sphygmomanometer in sitting, supine and standing positions. The left arm and same cuff sizes should be used for each measurement at all visits. If the left arm cannot be used at the screening visit or during the study for BP measurements, the reason should be documented and the right arm should be used for BP measurements for all subsequent visits.

    2. Change in Body Weight From Baseline at Week 24 in Subjects With a BMI ≥ 25 Kg/m2 [24 weeks]

      The body weight was obtained using a calibrated scale as part of complete physical examination or abbreviated physical examination.

    Other Outcome Measures

    1. Change From Baseline in Fasting Plasma Glucose (FPG) Over Time [24 weeks]

      The fasting plasma glucose (FPG) is measured at each study visit. The subject must have fasted for approximately 10 hours prior to the blood draw to ensure that the FPG value is truly a fasting sample.

    2. Change From Baseline of HbA1c From Baseline Over Time [24 weeks]

      Glycated hemoglobin A1c (%) was measured using an HPLC method in the laboratories that had completed NGSP Level I laboratory certification and were traceable to the Diabetes Control and Complications Trial (DCCT) reference method.

    3. Proportion of Subjects Who Achieve an HbA1c < 7% [Up to 24 weeks]

      Glycated hemoglobin A1c (%) was measured using an HPLC method in the laboratories that had completed NGSP Level I laboratory certification and were traceable to the Diabetes Control and Complications Trial (DCCT) reference method.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    The study population included:

    1. Male or female adult subjects ≥ 18 years of age at screening

    2. Subjects who were treatment naïve or receiving 1 OHA in combination with diet and exercise

    3. Subjects with a diagnosis of T2DM

    4. Subjects with HbA1c levels at screening between 7.0% and 10.5% (inclusive) if treatment-naïve or with HbA1c levels between 6.5 and 10.0% (inclusive) if on 1 oral anti diabetic agent

    5. Subjects with a BMI ≤ 45 kg/m2

    6. Subjects whose doses of medications for hypertension or hyperlipidemia (if applicable) had not changed for at least 30 days prior to screening

    7. Subjects who were willing and able to return for all clinic visits and to complete all study required procedures

    8. Female subjects of childbearing potential who were willing to use an adequate method of contraception and not become pregnant for the duration of the study.

    9. Subjects who maintained glycemic control throughout washout, if applicable.

    10. Subjects who had HbA1c levels between 7.0 and 10.5% prior to randomization

    11. Subjects who had been compliant in investigational product administration by missing no more than 1 dose of run-in medication

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

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

    2. Use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor agonist therapy) or thiazolidinedione class drugs at the time of screening

    3. Female subjects who were pregnant or breastfeeding

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

    5. Genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis) within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within 6 months from screening

    6. Estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL/min/1.73 m2 at screening

    7. Uncontrolled hypertension defined as a sitting systolic blood pressure >160 mm Hg or diastolic blood pressure > 95 mm Hg at screening

    8. A positive result for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV)

    9. History of alcohol or illicit drug abuse in the past 2 years

    10. Known human immunodeficiency virus (HIV) positive based on medical history

    11. Life expectancy < 2 years

    12. New York Heart Association (NYHA) Class IV heart failure within 3 months of screening

    13. MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening

    14. Treatment with an investigational drug within 30 days or within 7 half-lives of the investigational drug, whichever was longer

    15. Previous treatment with bexagliflozin or EGT0001474

    16. Use of any SGLT2 inhibitors, either at the time of screening or in the prior 3 months

    17. Currently participating in another interventional trial

    18. Not able to comply with the study scheduled visits

    19. Any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the primary investigator, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment

    20. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome at screening

    21. Two or more consecutive FPG measures ≥ 250 mg/dL (13.9 mmol/L) prior to randomization or 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

    22. At last visit prior to randomization, FPG level ≥ 250 mg/dL

    23. 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 Research Site Canoga Park California United States 91303
    2 Research Site Chino California United States 91710
    3 Research Site Huntington Park California United States 90255
    4 Research Site Los Angeles California United States 90057
    5 Research Site San Diego California United States 92103
    6 Research Site Fort Lauderdale Florida United States 33316
    7 Research Site Hialeah Florida United States 33012
    8 Research Site Miami Lakes Florida United States 33016
    9 Research Site Orlando Florida United States 32806
    10 Research Site Port Orange Florida United States 32127
    11 Research Site Trenton New Jersey United States 08611
    12 Research Site Calabash North Carolina United States 28467
    13 Research Site Morehead City North Carolina United States 28557
    14 Research Site Munroe Falls Ohio United States 44262
    15 Research Site Portland Oregon United States 97239
    16 Research Site North Myrtle Beach South Carolina United States 29582
    17 Research Site DeSoto Texas United States 75115
    18 Research Site Fort Worth Texas United States 76164
    19 Research Site Vancouver British Columbia Canada V6J 1S3
    20 Research Site Newmarket Ontario Canada L3Y 5G8
    21 Research Site 2 Toronto Ontario Canada M9V 4B4
    22 Research Site 1 Toronto Ontario Canada M9W 4L6
    23 Research Site Pointe-Claire Quebec Canada H9R 4S3

    Sponsors and Collaborators

    • Theracos

    Investigators

    • Study Director: J. Paul Lock, MD, Theracos

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Theracos
    ClinicalTrials.gov Identifier:
    NCT02715258
    Other Study ID Numbers:
    • THR-1442-C-450
    First Posted:
    Mar 22, 2016
    Last Update Posted:
    Jun 28, 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 A total of 210 subjects were randomized to be in the bexagliflozin arm or in the placebo arm in a ratio of 2:1.
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Period Title: Overall Study
    STARTED 140 70
    Intent to Treat/Safety Analysis 138 69
    COMPLETED 124 64
    NOT COMPLETED 16 6

    Baseline Characteristics

    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets Total
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks. Total of all reporting groups
    Overall Participants 138 69 207
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.8
    (10.21)
    54.7
    (11.02)
    55.4
    (10.47)
    Sex: Female, Male (Count of Participants)
    Female
    72
    52.2%
    35
    50.7%
    107
    51.7%
    Male
    66
    47.8%
    34
    49.3%
    100
    48.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    67
    48.6%
    40
    58%
    107
    51.7%
    Not Hispanic or Latino
    71
    51.4%
    29
    42%
    100
    48.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    15
    10.9%
    5
    7.2%
    20
    9.7%
    Native Hawaiian or Other Pacific Islander
    1
    0.7%
    0
    0%
    1
    0.5%
    Black or African American
    25
    18.1%
    6
    8.7%
    31
    15%
    White
    96
    69.6%
    58
    84.1%
    154
    74.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    0.7%
    0
    0%
    1
    0.5%
    Region of Enrollment (participants) [Number]
    Canada
    21
    15.2%
    12
    17.4%
    33
    15.9%
    United States
    117
    84.8%
    57
    82.6%
    174
    84.1%
    Body Weight at Baseline (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    90.5
    (20.48)
    84.6
    (19.75)
    88.6
    (20.39)
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    32.79
    (5.653)
    30.48
    (4.650)
    32.01
    (5.437)
    Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmHg]
    131.0
    (14.35)
    125.6
    (13.84)
    129.2
    (14.38)
    HbA1c (percentage of glycated hemoglobin) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of glycated hemoglobin]
    8.05
    (0.824)
    7.97
    (0.757)
    8.02
    (0.801)
    Fasting Plasma Glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mmol/L]
    9.39
    (1.957)
    9.45
    (2.079)
    9.41
    (1.994)
    Duration of Diabetes from Diagnosis to Screening (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    5.9
    (5.82)
    6.5
    (5.21)
    6.1
    (5.62)

    Outcome Measures

    1. Primary Outcome
    Title Change in HbA1c From Baseline at Week 24
    Description Glycated hemoglobin A1c (%) was measured using an HPLC method in the laboratories that had completed NGSP Level I laboratory certification and were traceable to the Diabetes Control and Complications Trial (DCCT) reference method.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Intention-to-Treat Population
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Measure Participants 138 69
    Least Squares Mean (Standard Error) [% of HbA1c]
    -0.51
    (0.082)
    -0.10
    (0.108)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Analysis of change from baseline in HbA1c (%) at Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0012
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.41
    Confidence Interval (2-Sided) 95%
    -0.66 to -0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 1: Multiple imputation for change from baseline in HbA1c (%) including observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0021
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.41
    Confidence Interval (2-Sided) 95%
    -0.68 to -0.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 2: Multiple imputation for change from baseline in HbA1c (%) excluding observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.55
    Confidence Interval (2-Sided) 95%
    -0.80 to -0.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 3: LOCF for change from baseline in HbA1c (%) including observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0009
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.64 to -0.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change in Systolic Blood Pressure (SBP) From Baseline at Week 24
    Description Blood pressure (BP) measurements are obtained using a calibrated sphygmomanometer in sitting, supine and standing positions. The left arm and same cuff sizes should be used for each measurement at all visits. If the left arm cannot be used at the screening visit or during the study for BP measurements, the reason should be documented and the right arm should be used for BP measurements for all subsequent visits.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT analysis set
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Measure Participants 138 69
    Least Squares Mean (Standard Error) [mmHg]
    -0.60
    (1.145)
    1.54
    (1.524)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Analysis of change from baseline in SBP (mm Hg) at Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2340
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -2.14
    Confidence Interval (2-Sided) 95%
    -5.66 to 1.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 1: Multiple imputation for change from baseline in SBP (mm Hg) including observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2937
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -1.91
    Confidence Interval (2-Sided) 95%
    -5.48 to 1.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 2: Multiple imputation for change from baseline in SBP (mm Hg) excluding observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4030
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -1.72
    Confidence Interval (2-Sided) 95%
    -5.75 to 2.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    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 0.2160
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -2.09
    Confidence Interval (2-Sided) 95%
    -5.41 to 1.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change in Body Weight From Baseline at Week 24 in Subjects With a BMI ≥ 25 Kg/m2
    Description The body weight was obtained using a calibrated scale as part of complete physical examination or abbreviated physical examination.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects with BMI >= 25 kg/m2 in the ITT analysis set
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Measure Participants 128 62
    Least Squares Mean (Standard Error) [Kg]
    -1.85
    (0.394)
    -1.06
    (0.485)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Analysis of change from baseline in body weight (kg) at Week 24 for subjects with BMI greater than or equal to 25 kg/m2
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1222
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.79
    Confidence Interval (2-Sided) 95%
    -1.80 to 0.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 1: Multiple imputation for change from baseline in body weight (kg) for subjects with BMI greater than or equal to 25 kg/m2 including observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2014
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.65
    Confidence Interval (2-Sided) 95%
    -1.65 to 0.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 2: Multiple imputation for change from baseline in body weight (kg) for subjects with BMI greater than or equal to 25 kg/m2 excluding observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0638
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.91
    Confidence Interval (2-Sided) 95%
    -1.88 to 0.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Sensitivity Analysis 3: LOCF for change from baseline in body weight (kg) for subjects with BMI greater than or equal to 25 kg/m2 including observations obtained after rescue medication
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1456
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -1.63 to 0.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Other Pre-specified Outcome
    Title Change From Baseline in Fasting Plasma Glucose (FPG) Over Time
    Description The fasting plasma glucose (FPG) is measured at each study visit. The subject must have fasted for approximately 10 hours prior to the blood draw to ensure that the FPG value is truly a fasting sample.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects with a value at baseline and Week 6, 12, 18 and 24
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Measure Participants 133 65
    Change from baseline at Week 6
    -1.40
    (2.116)
    0.50
    (2.655)
    Change from baseline at Week 12
    -1.41
    (1.904)
    0.33
    (2.103)
    Change from baseline at Week 18
    -1.17
    (2.058)
    0.03
    (2.337)
    Change from baseline at Week 24
    -1.02
    (2.013)
    -0.15
    (2.480)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Analysis of change from baseline in FPG (mmol/L) over time across 24 weeks
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -1.50
    Confidence Interval (2-Sided) 95%
    -1.92 to -1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Other Pre-specified Outcome
    Title Change From Baseline of HbA1c From Baseline Over Time
    Description Glycated hemoglobin A1c (%) was measured using an HPLC method in the laboratories that had completed NGSP Level I laboratory certification and were traceable to the Diabetes Control and Complications Trial (DCCT) reference method.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects with a value at baseline and at Week 6, 12, 18 and 24
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Measure Participants 133 65
    Change from baseline at Week 6
    -0.47
    (0.064)
    0.13
    (0.082)
    Change from baseline at Week 12
    -0.61
    (0.072)
    0.10
    (0.095)
    Change from baseline at Week 18
    -0.58
    (0.071)
    -0.01
    (0.093)
    Change from baseline at Week 24
    -0.51
    (0.082)
    -0.10
    (0.108)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Change from baseline in HbA1c (%) at Week 6
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.61
    Confidence Interval (2-Sided) 95%
    -0.79 to -0.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Change from baseline in HbA1c (%) at Week 12
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.71
    Confidence Interval (2-Sided) 95%
    -0.92 to -0.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Change from baseline in HbA1c (%) at Week 18
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.57
    Confidence Interval (2-Sided) 95%
    -0.78 to -0.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Change from baseline in HbA1c (%) at Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0012
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.41
    Confidence Interval (2-Sided) 95%
    -0.66 to -0.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Change from baseline in HbA1c (%) across 24 weeks
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments The mixed-effects repeated measures analysis includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter mixed-effects repeated measures
    Estimated Value -0.58
    Confidence Interval (2-Sided) 95%
    -0.76 to -0.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Other Pre-specified Outcome
    Title Proportion of Subjects Who Achieve an HbA1c < 7%
    Description Glycated hemoglobin A1c (%) was measured using an HPLC method in the laboratories that had completed NGSP Level I laboratory certification and were traceable to the Diabetes Control and Complications Trial (DCCT) reference method.
    Time Frame Up to 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects with a value at baseline and at Week 6, 12, 18 and 24
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject will receive bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject will receive placebo (inactive tablet) once daily for 24 weeks.
    Measure Participants 133 65
    Proportion of subjects with HbA1c < 7% at Week 6
    35
    25.4%
    6
    8.7%
    Proportion of subjects with HbA1c < 7% at Week 12
    44
    31.9%
    8
    11.6%
    Proportion of subjects with HbA1c < 7% at Week 18
    42
    30.4%
    10
    14.5%
    Proportion of subjects with HbA1c < 7% at Week 24
    41
    29.7%
    13
    18.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Bexagliflozin Tablets, 20 mg, Placebo Tablets
    Comments Model-Adjusted proportion of subjects with HbA1c <7% across 24 weeks
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments The logistic regression includes country, background anti-diabetes treatment status, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.39
    Confidence Interval (2-Sided) 95%
    1.69 to 6.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Adverse event data were collected from -8 weeks (V2) to 26 weeks (V12) according to the Schedule of Events outlined in the study protocol. Subjects in the Bexagliflozin group had mean study drug exposure of 22.52 weeks and the placebo group had mean mean study drug exposure of 22.90 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Bexagliflozin Tablets, 20 mg Placebo Tablets
    Arm/Group Description Each subject was to take bexagliflozin tablets, 20 mg once daily for 24 weeks. Each subject was to take placebo (inactive tablet) once daily for 24 weeks.
    All Cause Mortality
    Bexagliflozin Tablets, 20 mg Placebo Tablets
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/138 (0%) 1/69 (1.4%)
    Serious Adverse Events
    Bexagliflozin Tablets, 20 mg Placebo Tablets
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/138 (0.7%) 1/69 (1.4%)
    Cardiac disorders
    Cardiomyopathy 0/138 (0%) 0 1/69 (1.4%) 1
    Musculoskeletal and connective tissue disorders
    Tenosynovitis 1/138 (0.7%) 1 0/69 (0%) 0
    Other (Not Including Serious) Adverse Events
    Bexagliflozin Tablets, 20 mg Placebo Tablets
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 41/138 (29.7%) 25/69 (36.2%)
    Gastrointestinal disorders
    Abdominal pain 5/138 (3.6%) 6 5/69 (7.2%) 5
    Diarrhea 5/138 (3.6%) 5 5/69 (7.2%) 5
    Nausea 5/138 (3.6%) 5 2/69 (2.9%) 2
    General disorders
    Fatigue 5/138 (3.6%) 5 0/69 (0%) 0
    Infections and infestations
    Urinary tract infection 7/138 (5.1%) 7 2/69 (2.9%) 2
    Upper respiratory tract infection 5/138 (3.6%) 5 3/69 (4.3%) 3
    Metabolism and nutrition disorders
    Hyperglycemia 3/138 (2.2%) 3 3/69 (4.3%) 3
    Nervous system disorders
    Headache 4/138 (2.9%) 5 5/69 (7.2%) 5
    Renal and urinary disorders
    Polyuria 10/138 (7.2%) 10 2/69 (2.9%) 2
    Vascular disorders
    Hypertension 3/138 (2.2%) 4 5/69 (7.2%) 5

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Investigator does not have the right to publish the results.

    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:
    NCT02715258
    Other Study ID Numbers:
    • THR-1442-C-450
    First Posted:
    Mar 22, 2016
    Last Update Posted:
    Jun 28, 2021
    Last Verified:
    Jun 1, 2021