An Integrated Assessment of the Safety and Effectiveness of Bexagliflozin for the Management of Essential Hypertension

An Integrated Assessment of the Safety and Effectiveness of Bexagliflozin Tablets, 20 mg, for the Management of Essential Hypertension

This integrated assessment consists of two studies, 603A and 603B, to be carried out sequentially in a common study population. Participating subjects informed of the trial design and their consent to participate in both studies were to be obtained in a single consent form. Approximately 680 male or female adult subjects were to be enrolled.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Bexagliflozin; Drug: Placebo

Detailed Description

THR-1442-C-603 is an integrated assessment of the potential utility of bexagliflozin tablets, 20 mg for the treatment of essential hypertension. It is composed of two studies, 603A and 603B, measuring effects in a common population.

603A was a multicenter double-blind parallel group placebo-controlled study conducted to determine the placebo-adjusted change from baseline to week 12 in the mean ambulatory systolic blood pressure (SBP) of approximately 680 subjects considered generally representative of the adult hypertensive population in the United States. Secondary endpoints included the placebo-adjusted change from baseline to week 12 of the mean office seated systolic blood pressure, the change to week 12 of the mean ambulatory and mean office seated diastolic blood pressure, the proportion of subjects achieving prespecified goals for absolute systolic and diastolic blood pressure as well as prespecified goals for reduction in systolic and diastolic blood pressure, measured by ambulatory and seated office measurement methodology.

A603B was a multicenter double-blind parallel group placebo-controlled randomized withdrawal study conducted to determine the durability of the antihypertensive effect of bexagliflozin tablets, 20 mg, in a population not pre-selected for existing diabetes. All subjects entered a 12 week run-in period during which they self-administered open label bexagliflozin tablets, 20 mg once daily. At week 12 a baseline ambulatory blood pressure monitoring (ABPM) measurement was made, and the subjects were randomized one to one to receive either bexagliflozin tablets, 20 mg or bexagliflozin tablets, placebo. After a 12 week treatment period a second ABPM measurement was made. The primary endpoint was the intergroup difference in the change from baseline in the mean SBP.

• Study Type: Interventional
• Enrollment (Actual): 673
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Clinical Research Site
    • Birmingham, Alabama, United States, 35211
      • Clinical Research Site
    • Birmingham, Alabama, United States, 35242
      • Clinical Research Site
    • Foley, Alabama, United States, 36535
      • Clinical Research Site
    • Gulf Shores, Alabama, United States, 36542
      • Clinical Research Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Clinical Research Site
    • Mesa, Arizona, United States, 85206
      • Clinical Research Site
    • Phoenix, Arizona, United States, 85020
      • Clinical Research Site
    • Tucson, Arizona, United States, 85741
      • Clinical Research Site
  • California
    • Anaheim, California, United States, 92801
      • Clinical Research Site
    • Bellflower, California, United States, 90706
      • Clinical Research Site
    • Fair Oaks, California, United States, 95628
      • Clinical Research Site
    • Fresno, California, United States, 93702
      • Clinical Research Site
    • Lincoln, California, United States, 95648
      • Clinical Research Site
    • Los Angeles, California, United States, 90057
      • Clinical Research Site
    • San Gabriel, California, United States, 91776
      • Clinical Research Site
    • Santa Rosa, California, United States, 95405
      • Clinical Research Site
    • Upland, California, United States, 91786
      • Clinical Research Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Clinical Research Site
    • Colorado Springs, Colorado, United States, 80918
      • Clinical Research Site
    • Denver, Colorado, United States, 80246
      • Clinical Research Site
    • Golden, Colorado, United States, 80401
      • Clinical Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Clinical Research Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Clinical Research Site
    • Decatur, Georgia, United States, 30032
      • Clinical Research Site
    • Lithonia, Georgia, United States, 30058
      • Clinical Research Site
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Clinical Research Site
    • Chicago, Illinois, United States, 60611
      • Clinical Research Site
    • Chicago, Illinois, United States, 60616
      • Clinical Research Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Clinical Research Site
    • Evansville, Indiana, United States, 47714
      • Clinical Research Site
    • Indianapolis, Indiana, United States, 46260
      • Clinical Research Site
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Clinical Research Site
  • Kansas
    • Prairie Village, Kansas, United States, 66208
      • Clinical Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Clinical Research Site
    • Paducah, Kentucky, United States, 42003
      • Clinical Research Site
    • Versailles, Kentucky, United States, 40383
      • Clinical Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Clinical Research Site
  • Maine
    • Auburn, Maine, United States, 04210
      • Clinical Research Site
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Clinical Research Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Clinical Research Site
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Clinical Research Site
    • Saint Louis, Missouri, United States, 63141
      • Clinical Research Site
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Clinical Research Site
    • Las Vegas, Nevada, United States, 89128
      • Clinical Research Site
  • New Jersey
    • Trenton, New Jersey, United States, 08611
      • Clinical Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Clinical Research Site
  • New York
    • Bronx, New York, United States, 10455
      • Clinical Research Site
    • Brooklyn, New York, United States, 11230
      • Clinical Research Site
    • Hartsdale, New York, United States, 10530
      • Clinical Research Site
  • North Carolina
    • Shelby, North Carolina, United States, 28150
      • Clinical Research Site
  • Ohio
    • Akron, Ohio, United States, 44311
      • Clinical Research Site
    • Cincinnati, Ohio, United States, 45236
      • Clinical Research Site
    • Cincinnati, Ohio, United States, 45245
      • Clinical Research Site
    • Columbus, Ohio, United States, 43213
      • Clinical Research Site
    • Dayton, Ohio, United States, 45439
      • Clinical Research Site
    • Dublin, Ohio, United States, 43215
      • Clinical Research Site
    • Grove City, Ohio, United States, 43214
      • Clinical Research Site
    • Lyndhurst, Ohio, United States, 44124
      • Clinical Research Site
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Clinical Research Site
    • Oklahoma City, Oklahoma, United States, 73119
      • Clinical Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Clinical Research Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Clinical Research Site
    • Hatboro, Pennsylvania, United States, 19040
      • Clinical Research Site
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Clinical Research Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Clinical Research Site 2
    • Anderson, South Carolina, United States, 29621
      • Clinical Research Site
    • Greer, South Carolina, United States, 29650
      • Clinical Research Site
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Clinical Research Site
    • Knoxville, Tennessee, United States, 37909
      • Clinical Research Site
  • Texas
    • Arlington, Texas, United States, 76014
      • Clinical Research Site
    • Dallas, Texas, United States, 75231
      • Clinical Research Site
    • Houston, Texas, United States, 77070
      • Clinical Research Site
    • Kingwood, Texas, United States, 77339
      • Clinical Research Site
    • Mesquite, Texas, United States, 75143
      • Clinical Research Site
    • Plano, Texas, United States, 75093
      • Clinical Research Site
    • San Antonio, Texas, United States, 78229
      • Clinical Research Site
    • Tomball, Texas, United States, 77375
      • Clinical Research Site
  • Utah
    • Layton, Utah, United States, 84041
      • Clinical Research Site
    • Murray, Utah, United States, 84123
      • Clinical Research Site
    • West Jordan, Utah, United States, 84088
      • Clinical Research Site
  • Virginia
    • Arlington, Virginia, United States, 22207
      • Clinical Research Site
    • Burke, Virginia, United States, 22015
      • Clinical Research Site
    • Charlottesville, Virginia, United States, 22911
      • Clinical Research Site
    • Danville, Virginia, United States, 24541
      • Clinical Research Site
    • Manassas, Virginia, United States, 20110
      • Clinical Research Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

To be eligible for randomization a prospective subject was to be:

• Male or female of age ≥ 20 years
• Diagnosed with essential hypertension and exhibiting an office seated SBP ≥ 140 and < 180 mm Hg
• Unmedicated or prescribed no more than 4 agents for hypertension. Unmedicated subjects were subjects who had never taken medications for hypertension or had not taken any anti-hypertensive medication for at least 3 months. A stable dose meant no change in dose or frequency had taken place in the 4 weeks prior to the screening visit
• If female and of childbearing potential, willing to use an adequate method of contraception and to not become pregnant for the duration of the study.
• Willing and able to return for all clinic visits and to complete all study-required procedures
• Able to self-medicate during the run-in period, omitting no more than one day of dosing
• Shown to have a seated SBP ≥ 140 and < 180 mm Hg
• Shown to exhibit a mean 24 h SBP ≥ 135 mm Hg

Prospective participants exhibiting any of the following characteristics were to be excluded from the study:

• Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young (MODY)
• Known history of secondary or malignant hypertension
• Seated diastolic blood pressure (DBP) >110 mm Hg at screening
• Taking insulin for diabetes
• Prescribed more than 4 anti-hypertension medications
• Having a genitourinary tract infection within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within the last 6 months
• Having cancer, active or in remission for < 3 years
• History of alcohol or illicit drug abuse in the past 2 years
• History of myocardial infarction, stroke or hospitalization for heart failure in the prior 6 months
• Previous exposure to bexagliflozin or EGT0001474
• History of hypertensive emergency
• History of sodium glucose linked transporter 2 (SGLT2) inhibitor treatment in the last 3 months
• Known intolerance or allergy to SGTL2 inhibitors
• Any condition, disease, disorder, or clinically relevant laboratory abnormality that, in the opinion of the PI, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment
• Pregnancy or nursing
• Current participation in another interventional trial or having been exposed to an investigational drug within 30 days or 7 half-lives of screening, whichever is longer
• Arm circumference too large or small to allow accurate ambulatory monitoring
• History of kidney transplant
• Occupational or other lifestyle factors that could hamper the collection of valid ABPM data
• Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase > 1.5 × upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN
• Estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), < 45 mL/min/1.73 m2 or requiring dialysis
• HbA1c > 9.5%
• Positive urine pregnancy test for female subjects of child bearing potential
• Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase > 1.5 × upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN
• eGFR, as calculated by the modification of diet in renal disease study equation (MDRD), < 45 mL/min/1.73 m2 or requiring dialysis
• HbA1c > 9.5%
• Positive urine pregnancy test for female subjects of child bearing potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence 1; Period 1: Placebo Period 2: Bexagliflozin Period 3: Bexagliflozin	Drug: Bexagliflozin; Bexagliflozin tablet, 20 mg; Other Names: EGT0001442; Drug: Placebo; Placebo (inactive) tablet to match the active drug
Other: Sequence 2; Period 1: Placebo Period 2: Bexagliflozin Period 3: Placebo	Drug: Bexagliflozin; Bexagliflozin tablet, 20 mg; Other Names: EGT0001442; Drug: Placebo; Placebo (inactive) tablet to match the active drug
Other: Sequence 3; Period 1: Bexagliflozin Period 2: Bexagliflozin Period 3: Bexagliflozin	Drug: Bexagliflozin; Bexagliflozin tablet, 20 mg; Other Names: EGT0001442
Other: Sequence 4; Period 1: Bexagliflozin Period 2: Bexagliflozin Period 3: Placebo	Drug: Bexagliflozin; Bexagliflozin tablet, 20 mg; Other Names: EGT0001442; Drug: Placebo; Placebo (inactive) tablet to match the active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12	Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared to placebo	Baseline (Day 1) to week 12
Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36	Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared placebo	Change from week 24 to week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
603A, Reduction of Mean Ambulatory Systolic Blood Pressure	Proportion of subjects who achieve a reduction of mean ambulatory systolic blood pressure of 10 mm Hg or greater	Baseline (Day 1) to week 12
603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less	Proportion of subjects who achieve a mean ambulatory systolic blood pressure of 135 mm Hg or less	Baseline (Day 1) to week 12
603A, Change in Seated Office Systolic Blood Pressure	Placebo-adjusted change in seated office systolic blood pressure	Baseline (Day 1) to week 12
603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less	Proportion of subjects who achieve a seated office systolic blood pressure of 140 mm Hg or less	Baseline (Day 1) to week 12
603A, Change in Mean Ambulatory Diastolic Blood Pressure	Placebo-adjusted change in mean ambulatory diastolic blood pressure	Baseline (Day 1) to week 12
603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less	Proportion of subjects who achieve a mean ambulatory diastolic blood pressure of 87 mm Hg or less	Baseline (Day 1) to week 12
603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater	Proportion of subjects who achieve a reduction of mean ambulatory diastolic blood pressure of 4 mm Hg or greater	Baseline (Day 1) to week 12
603A, Change in Seated Office Diastolic Blood Pressure	Placebo-adjusted change in seated office diastolic blood pressure	Baseline (Day 1) to week 12
603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less	Proportion of subjects who achieve a mean seated office diastolic blood pressure of 90 mm Hg or less	Baseline (Day 1) to week 12
603B, Change in Seated Office Systolic Blood Pressure	Placebo-adjusted change from week 12 to week 24 in seated office systolic blood pressure	Week 12 (cumulative week 24) to Week 24 (cumulative week 36)
603B, Change in Mean Ambulatory Diastolic Blood Pressure	Placebo-adjusted change in mean ambulatory diastolic blood pressure	Week 12 (cumulative week 24) to Week 24 (cumulative week 36)
603B, Change in Seated Office Diastolic Blood Pressure	Placebo-adjusted change from week 12 to week 24 in seated office diastolic blood pressure	Week 12 (cumulative week 24) to Week 24 (cumulative week 36)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure	Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on mean ambulatory systolic and diastolic blood pressure after 12 weeks of bexagliflozin treatment, as well as longer treatment periods, i.e., 24 weeks or 36 weeks of bexagliflozin treatment.	Baseline (Day 1) to cumulative week 36
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure	Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on seated office systolic and diastolic blood pressure over time	Baseline (Day 1) to cumulative week 36

Collaborators and Investigators

• Sponsor: Theracos
• Investigators: Study Director: Andrew Allegretti, M.D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2017
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: November 8, 2017
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 2, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Hypoglycemic Agents; Physiological Effects of Drugs; Bexagliflozin
• Other Study ID Numbers: THR-1442-C-603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No