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History of Changes for Study: NCT02558296
Effects of Bexagliflozin on HbA1c in Patients With Type 2 Diabetes and Increased Risk of Cardiovascular Adverse Events (BEST)
Latest version (submitted July 13, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 22, 2015 None (earliest Version on record)
2 November 19, 2015 Recruitment Status, Study Status, Contacts/Locations, Arms and Interventions, Oversight and Study Identification
3 January 5, 2016 Study Status and Contacts/Locations
4 January 7, 2016 Contacts/Locations and Study Status
5 February 25, 2016 Contacts/Locations, Study Status, References, IPDSharing and Eligibility
6 March 11, 2016 Contacts/Locations, Study Status and Study Description
7 May 16, 2016 Contacts/Locations and Study Status
8 September 23, 2016 Contacts/Locations and Study Status
9 December 19, 2016 Contacts/Locations and Study Status
10 March 8, 2017 Contacts/Locations and Study Status
11 July 5, 2017 Contacts/Locations and Study Status
12 February 12, 2018 Recruitment Status, Contacts/Locations and Study Status
13 April 3, 2018 Study Design and Study Status
14 December 17, 2018 Study Status
15 June 4, 2019 Study Status and Study Design
16 August 15, 2019 Study Status
17 August 23, 2019 Study Status
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Results Submission Events
18 June 15, 2021 Recruitment Status, Study Status, Outcome Measures, Document Section, Results and Study Identification
19 July 13, 2021 Study Status, Outcome Measures
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Study NCT02558296
Submitted Date:  September 22, 2015 (v1)
Open or close this module Study Identification
Unique Protocol ID: THR-1442-C-476
Brief Title: Effects of Bexagliflozin on HbA1c in Patients With Type 2 Diabetes and Increased Risk of Cardiovascular Adverse Events (BEST)
Official Title: A Double Blind Placebo Controlled Study to Evaluate the Effects of Bexagliflozin on Hemoglobin A1c in Patients With Type 2 Diabetes and Increased Risk of Cardiovascular Adverse Events
Secondary IDs:
Open or close this module Study Status
Record Verification: September 2015
Overall Status: Not yet recruiting
Study Start: October 2015
Primary Completion: October 2018 [Anticipated]
Study Completion: April 2019 [Anticipated]
First Submitted: September 22, 2015
First Submitted that
Met QC Criteria:		 September 22, 2015
First Posted: September 23, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:		 September 22, 2015
Last Update Posted: September 23, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Theracos
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module 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) and increased risk of cardiovascular adverse events.

The data from this study will be combined with the data from other bexagliflozin studies in a meta-analysis of CV safety outcomes.
Detailed Description:

Approximately 130 investigative sites globally are planned to participate in this study.

An estimated 1650 subjects with poorly controlled T2DM and an elevated risk of cardiovascular adverse events will be randomized to bexagliflozin tablets, 20 mg, or placebo in a ratio of 2:1 in addition to the background anti-diabetic medications.

The study is an event-driven trial. The treatment period will end when the last randomized subject has completed at least 52 weeks of treatment and a total of at least 134 subjects have experienced a cardiac event.
Open or close this module Conditions
Conditions: Type 2 Diabetes Mellitus
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 1650 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Bexagliflozin tablets, 20 mg
Each subject will receive bexagliflozin 20 mg once daily for the duration of the study.
 Drug: Bexagliflozin
20 mg, tablet
Other Names:
  • EGT0001442, EGT0001474
Placebo Comparator: Placebo tablets
Each subject will receive placebo (inactive tablet) once daily for the duration of the study.
 Drug: Placebo
20 mg tablet to match active comparator
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Change in HbA1c from baseline to week 24
[ Time Frame: 24 weeks ]

The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with increased risk of cardiovascular adverse events.
Secondary Outcome Measures:
1. Change in body weight from baseline to week 48
[ Time Frame: 48 weeks ]

To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48in randomized subjects with a BMI ≥ 25 kg/m2 compared to placebo
2. Change in systolic blood pressure from baseline to week 24
[ Time Frame: 24 weeks ]

To evaluate the effect of 20 mg bexagliflozin on the change in systolic blood pressure (SBP) from baseline to week 24 in subjects with baseline systolic blood pressure ≥ 140 mmHg compared to placebo
Other Outcome Measures:
1. Change in HbA1c over time
[ Time Frame: Duration of study ]

To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c versus placebo over time
2. Change in fasting plasma glucose over time
[ Time Frame: Duration of study ]

To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time
3. Proportion of subjects requiring an intensification of anti-diabetic regimen over time
[ Time Frame: Duration of study ]

To measure the proportion of subjects requiring an intensification of anti-diabetic regimen versus placebo over time
4. Proportion of subjects requiring a relaxation of their anti-diabetic regimen over time
[ Time Frame: Duration of study ]

To measure the proportion of subjects requiring a relaxation of their anti-diabetic regimen versus placebo over time
5. Incidence of hospitalization for heart failure
[ Time Frame: Duration of study ]

To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline
6. Evaluation of the safety of exposure to bexagliflozin for a minimum of 52 weeks
[ Time Frame: At least 52 weeks ]

An additional safety objective will be to evaluate the safety of exposure to bexagliflozin for a minimum of 52 weeks in a treatment population that is at elevated risk for major adverse cardiovascular events.
7. Bexagliflozin plasma concentration over time for population pharmacokinetics study
[ Time Frame: 12 weeks ]

As part of an additional pharmacokinetic study, measurement of bexagliflozin plasma concentration as a function of time from dosing (sparsely sampled) will be conducted at 30 sites and will include approximately 240 subjects.
Open or close this module Eligibility
Minimum Age: 40 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Male or female age ≥40 years
  2. Subjects with a diagnosis of T2DM
  3. Subjects with HbA1c values of 7.5 - 11%, inclusive
  4. Subjects with fasting plasma glucose ≤ 250 mg/dL at screening
  5. Subjects who have a regimen for treatment of T2DM that has been stable for the past 3 months
  6. Subjects who present with at least one of the following 3 histories:

    Group 1: A history of atherosclerotic vascular disease

    Group 2: A history of heart failure

    Group 3: Age ≥ 55 years with diabetes for ≥ 10 years, uncontrolled hypertension, currently smoking, reduced kidney function, or cholesterol problems

  7. Female subjects of childbearing potential who are willing to use an adequate method of contraception and to not become pregnant for the duration of the study
  8. Subjects who are willing and able to return for all clinic visits and to complete all study-required procedures, including self-monitored blood glucose measurement
  9. Subjects who receive anti-hypertensive medications at a stable dosage for ≥ 2 weeks prior to randomization
  10. Subjects who receive lipid modifying therapy on a stable regimen for 6 weeks prior to randomization
  11. Subjects who have SBP < 170 mmHg and DBP < 110 mmHg at screening.

Exclusion Criteria:

  1. Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young
  2. Hemoglobinopathy that affects HbA1c measurement
  3. Frequent symptomatic hypoglycemia
  4. Genitourinary tract infection within 6 weeks of screening or history of genitourinary infections
  5. Cancer, active or in remission for < 3 years
  6. History of alcohol or illicit drug abuse in the past 2 years
  7. Evidence of abnormal liver function
  8. History of MI, stroke or hospitalization for heart failure in the prior 3 months
  9. Presently scheduled for heart surgery
  10. Prior kidney transplant or evidence of kidney problems
  11. Prior or planned pace maker implantation
  12. Pregnant or nursing
  13. Currently participating in another interventional trial Previous treatment with bexagliflozin or EGT0001474
  14. Currently or within 3 months of taking any SGLT2 inhibitors
  15. Any condition, disease, disorder, or clinically relevant laboratory abnormality that, in the opinion of the principle investigator, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment
Open or close this module Contacts/Locations
Central Contact Person: Roger Albright
Telephone: 617-643-5696
Email: ralbright@ccib.mgh.harvard.edu
Central Contact Backup: Yuan-Di C. Halvorsen, Ph. D.
Telephone: 617-726-4236
Email: yhalvorsen@ccib.mgh.harvard.edu
Study Officials: Geoffrey A. Walford, M. D.
Study Director
Massachusetts General Hospital
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations: UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998 Sep 12;317(7160):703-13. Erratum In: BMJ 1999 Jan 2;318(7175):29. PubMed 9732337
American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care. 2013 Jan;36 Suppl 1(Suppl 1):S11-66. doi: 10.2337/dc13-S011. No abstract available. PubMed 23264422
American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available. PubMed 24357209
Aronow WS, Ahn C. Incidence of heart failure in 2,737 older persons with and without diabetes mellitus. Chest. 1999 Mar;115(3):867-8. doi: 10.1378/chest.115.3.867. PubMed 10084505
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Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979 May 11;241(19):2035-8. doi: 10.1001/jama.241.19.2035. PubMed 430798
Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther. 2014 Sep 11;8:1335-80. doi: 10.2147/DDDT.S50773. eCollection 2014. PubMed 25246775
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Preis SR, Hwang SJ, Coady S, Pencina MJ, D'Agostino RB Sr, Savage PJ, Levy D, Fox CS. Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005. Circulation. 2009 Apr 7;119(13):1728-35. doi: 10.1161/CIRCULATIONAHA.108.829176. Epub 2009 Mar 23. PubMed 19307472
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