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

• ClinicalTrials.gov Identifier: NCT02715258
• Recruitment Status: Completed
• First Posted: March 22, 2016
• Results First Posted: April 28, 2021
• Last Update Posted: June 28, 2021
• Sponsor: Theracos
• Information provided by (Responsible Party): Theracos

Tracking Information

• First Submitted Date: March 11, 2016
• First Posted Date: March 22, 2016
• Results First Submitted Date: April 1, 2021
• Results First Posted Date: April 28, 2021
• Last Update Posted Date: June 28, 2021
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2021)

Change in HbA1c From Baseline at Week 24 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: March 16, 2016): Change in HbA1c from baseline to week 24 [ Time Frame: 24 weeks ]

Current Secondary Outcome Measures (submitted: April 1, 2021)

• Change in Systolic Blood Pressure (SBP) From Baseline at Week 24 [ Time Frame: 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.
• Change in Body Weight From Baseline at Week 24 in Subjects With a BMI ≥ 25 Kg/m2 [ Time Frame: 24 weeks ]
  The body weight was obtained using a calibrated scale as part of complete physical examination or abbreviated physical examination.

Original Secondary Outcome Measures (submitted: March 16, 2016)

• Change in systolic blood pressure from baseline to week 24 [ Time Frame: 24 weeks ]
• Change in body weight from baseline to week 24 [ Time Frame: 24 weeks ]

Current Other Pre-specified Outcome Measures (submitted: April 1, 2021)

• Change From Baseline in Fasting Plasma Glucose (FPG) Over Time [ Time Frame: 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.
• Change From Baseline of HbA1c From Baseline Over Time [ Time Frame: 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.
• Proportion of Subjects Who Achieve an HbA1c < 7% [ Time Frame: 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.

Original Other Pre-specified Outcome Measures (submitted: March 16, 2016)

• Change from baseline of fasting plasma glucose from baseline up to 24 weeks [ Time Frame: 24 weeks ]
• Change from baseline of HbA1c from baseline up to 24 weeks [ Time Frame: 24 weeks ]
• Proportion of subjects who achieve an HbA1c < 7% [ Time Frame: Up to 24 weeks ]
• Safety of exposure to bexagliflozin for 24 weeks (adverse events) [ Time Frame: 24 weeks ]
  Safety will be assessed based on an analysis of the adverse events record; of laboratory data, including hematology, serum chemistry, urinalysis, urinary electrolytes and creatinine; of electrocardiograms (ECGs), vital signs and physical examinations; and of concomitant medication use. All subjects who are randomized and take at least one dose of double-blind study medication will be included in the Safety Analysis Set. Safety analyses will be based on the medication that was actually dispensed to each subject.
• Effect of bexagliflozin on the incidence of adverse events of special interest [ Time Frame: 24 weeks ]

Descriptive Information

• Brief Title: Safety and Efficacy of Bexagliflozin as Monotherapy in Patients With Type 2 Diabetes
• 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
• 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).

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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus

Intervention

• Drug: Bexagliflozin
  tablets containing 20 mg bexagliflozin
  Other Name: EGT0001442
• Drug: Placebo
  tablets matching the appearance of bexagliflozin tablets

Study Arms

• Active Comparator: Bexagliflozin tablets, 20 mg
  Each subject will self-administer bexagliflozin tablets once daily for 24 weeks.
  Intervention: Drug: Bexagliflozin
• Placebo Comparator: Placebo tablets
  Each subject will self-administer placebo (inactive tablet) once daily for 24 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 16, 2016): 210
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2017
• Actual Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02715258
• Other Study ID Numbers: THR-1442-C-450
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Theracos
• Original Responsible Party: Same as current
• Current Study Sponsor: Theracos
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Theracos
• Verification Date: June 2021