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The purpose of this study is to investigate the effect of bexagliflozin compared to glimepiride as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with type 2 diabetes mellitus (T2DM).
Approximately 420 subjects with inadequately controlled T2DM on metformin will be recruited from North America and Europe. Subjects will be randomly assigned to receive bexagliflozin tablets, 20 mg, or glimepiride capsules, 2, 4 or 6 mg, in a ratio of 1:1 once daily for 96 weeks. Subjects will continue to take metformin for the duration of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bexagliflozin | Active Comparator | Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride daily for the duration of the study. |
|
| Glimepiride | Active Comparator | Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bexagliflozin | Drug | 20 mg, tablet |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in HbA1c at Week 60 | The primary objective is to demonstrate that bexagliflozin is non-inferior to glimepiride by evaluating the treatment effect on HbA1c reduction at week 60 in subjects whose T2DM is inadequately controlled by metformin. The least square mean (LSM) change from baseline to Week 60 was analyzed using a mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA). | Baseline and Week 60 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Body Weight at Week 60 for Subjects With Baseline BMI ≥ 25 kg/m2 | Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of body weight in subjects with baseline BMI ≥ 25 kg/m2 at week 60 is analyzed using ANCOVA. | Baseline and 60 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J. Paul Lock, MD | Theracos Sub, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Birmingham | Alabama | 35205 | United States | ||
| Research Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bexagliflozin | Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 27, 2016 | Apr 15, 2020 |
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| Placebo for Bexagliflozin | Drug | inactive tablet to match active comparator bexagliflozin |
|
| Glimepiride | Drug | 2, 4 or 6 mg, capsule |
|
| Placebo for Glimepiride | Drug | inactive capsules to match active comparator glimepiride |
|
| Change From Baseline in Systolic Blood Pressure (SBP) at Week 60 for Subjects With Baseline SBP ≥ 140 mmHg |
Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of SBP in subjects with baseline SBP ≥ 140 mmHg at week 60 is analyzed using ANCOVA. |
| Baseline and 60 weeks |
| Difference in Proportion of Subjects With ≥ 1 Severe or Documented Symptomatic Hypoglycemia Events Over 96 Weeks | The difference in proportion of subjects with ≥ 1 severe or documented symptomatic hypoglycemia events in the bexagliflozin group compared with glimepiride group over 96 weeks is analyzed using a logistic regression model. The full model included region, baseline HbA1c value, background treatment status (metformin or metformin + OHA), eGFR at baseline ≥ 90 or < 90 mL min 1 per 1.73 m2), treatment as a fixed effect covariate. | During the 96 week treatment period |
| Superiority of Bexagliflozin Over Glimepiride in HbA1c Reduction at Week 60. | Superiority of bexagliflozin over glimepiride in HbA1c reduction from baseline to week 60 will be declared if the upper bound of 95% CI is less than 0. | Baseline to Week 60 |
| Huntington Park |
| California |
| 90255 |
| United States |
| Research Site | Los Angeles | California | 90057 | United States |
| Research Site | San Carlos | California | 94070 | United States |
| Research Site | Hialeah | Florida | 33012 | United States |
| Research Site | Miami Lakes | Florida | 33016 | United States |
| Research Site | Orlando | Florida | 32806 | United States |
| Research Site | West Palm Beach | Florida | 33401 | United States |
| Research Site | Calabash | North Carolina | 28467 | United States |
| Research Site | Morehead City | North Carolina | 28557 | United States |
| Research Site | Magnolia | Texas | 77355 | United States |
| Research Site | Aschaffenburg | 63739 | Germany |
| Research Site | Essen | 45277 | Germany |
| Research Site 2 | Essen | 45355 | Germany |
| Research Site 2 | Hamburg | 21073 | Germany |
| Research Site | Hamburg | 22607 | Germany |
| Research Site | Heidelberg | 69115 | Germany |
| Research Site | Magdeburg | 39120 | Germany |
| Research Site | Wangen | 88239 | Germany |
| Research Site | Bochnia | 32-700 | Poland |
| Research Site | Bydgoszcz | 85-312 | Poland |
| Research Site | Krakow | 30-015 | Poland |
| Research Site 2 | Krakow | 31-011 | Poland |
| Research Site | Lodz | 90-242 | Poland |
| Research Site 2 | Lublin | 20-064 | Poland |
| Research Site | Lublin | 20-362 | Poland |
| Research Site | Olsztyn | 10-117 | Poland |
| Research Site | Poznan | 61-655 | Poland |
| Research Site | Puławy | 24-100 | Poland |
| Research Site | Staszów | 28-200 | Poland |
| Research Site | Swarzędz | 62-020 | Poland |
| Research Site | Świdnik | 21-040 | Poland |
| Research Site | Torun | 87-100 | Poland |
| Research Site | Warsaw | 00-660 | Poland |
| Research Site | Zamość | 22-400 | Poland |
| Research Site | Alicante | Spain |
| Research Site 2 | Barcelona | Spain |
| Research Site | Barcelona | Spain |
| Research Site 2 | Madrid | Spain |
| Research Site 3 | Madrid | Spain |
| Research Site | Madrid | Spain |
| Research Site 2 | Málaga | Spain |
| Research Site | Málaga | Spain |
| Research Site 2 | Oviedo | Spain |
| Research Site | Valencia | Spain |
| Glimepiride |
Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg |
| Study Complete at Week 60 |
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| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bexagliflozin | Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator |
| BG001 | Glimepiride | Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | cm |
| |||||||||||||||
| Body Weight at Baseline | Mean | Standard Deviation | kg |
| |||||||||||||||
| BMI | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||
| Systolic Blood Pressure at Baseline | Mean | Standard Deviation | mm Hg |
| |||||||||||||||
| Systolic Blood Pressure Categories | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in HbA1c at Week 60 | The primary objective is to demonstrate that bexagliflozin is non-inferior to glimepiride by evaluating the treatment effect on HbA1c reduction at week 60 in subjects whose T2DM is inadequately controlled by metformin. The least square mean (LSM) change from baseline to Week 60 was analyzed using a mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA). | The intention-to-treat population was used for the analysis. Subjects with a value at baseline and at week 60 were analyzed. | Posted | Least Squares Mean | Standard Error | percentage of glycated hemoglin | Baseline and Week 60 |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Body Weight at Week 60 for Subjects With Baseline BMI ≥ 25 kg/m2 | Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of body weight in subjects with baseline BMI ≥ 25 kg/m2 at week 60 is analyzed using ANCOVA. | Number of subjects with a value at baseline and at the specified visit | Posted | Least Squares Mean | Standard Error | kg | Baseline and 60 weeks |
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| Secondary | Change From Baseline in Systolic Blood Pressure (SBP) at Week 60 for Subjects With Baseline SBP ≥ 140 mmHg | Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of SBP in subjects with baseline SBP ≥ 140 mmHg at week 60 is analyzed using ANCOVA. | Posted | Least Squares Mean | Standard Error | mm Hg | Baseline and 60 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Difference in Proportion of Subjects With ≥ 1 Severe or Documented Symptomatic Hypoglycemia Events Over 96 Weeks | The difference in proportion of subjects with ≥ 1 severe or documented symptomatic hypoglycemia events in the bexagliflozin group compared with glimepiride group over 96 weeks is analyzed using a logistic regression model. The full model included region, baseline HbA1c value, background treatment status (metformin or metformin + OHA), eGFR at baseline ≥ 90 or < 90 mL min 1 per 1.73 m2), treatment as a fixed effect covariate. | Subjects with post-baseline assessment. | Posted | Number | 95% Confidence Interval | Proportion of participants | During the 96 week treatment period |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Superiority of Bexagliflozin Over Glimepiride in HbA1c Reduction at Week 60. | Superiority of bexagliflozin over glimepiride in HbA1c reduction from baseline to week 60 will be declared if the upper bound of 95% CI is less than 0. | The intention-to-treat population was used for the analysis. Subjects with a value at baseline and at week 60 were analyzed. | Posted | Least Squares Mean | Standard Error | percentage of glycated hemoglobin | Baseline to Week 60 |
|
|
Adverse event data was collected from Week -8 (V2, wash-out) to Week 98 (V18, follow-up).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bexagliflozin | Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator | 0 | 213 | 25 | 213 | 98 | 213 |
| EG001 | Glimepiride | Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg | 1 | 213 | 26 | 213 | 112 | 213 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
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| Myocardial ischemia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
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| Acute coronary syndrome | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Myocarditis | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Palpitation | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Erysipelas | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Otitis media chronic | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Transient ischemic attack | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Carotid artery stenosis | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Ischemic stroke | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Nervous system disorder | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Thalamic infarction | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Osteochondrosis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Polyarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Ankle fracture | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Contusion | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Muscle rupture | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Tibia fracture | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Ectropion | Eye disorders | MedDRA 19.0 | Systematic Assessment |
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| Entropion | Eye disorders | MedDRA 19.0 | Systematic Assessment |
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| Retinal detachment | Eye disorders | MedDRA 19.0 | Systematic Assessment |
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| Faecaloma | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Inguinal hernia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
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| Bladder disorder | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rectal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
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| Small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
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| Genital hemorrhage | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
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| Uterine prolapse | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Phimosis | Congenital, familial and genetic disorders | MedDRA 19.0 | Systematic Assessment |
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| Deafness unilateral | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
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| Arterial occlusive disease | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
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| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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Investigator has no publication right.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Albert Collinson | Theracos Sub, LLC | (508) 630-2129 | acollinson@theracos.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 24, 2019 | Apr 15, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C000705992 | bexagliflozin |
| C057619 | glimepiride |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Poland |
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| Germany |
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| Spain |
|
| > 140 mm Hg |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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