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

NCT ID: NCT03514641

Last Updated: 2021-09-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

673 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-18

Study Completion Date

2018-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Essential Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The primary endpoint of study 603A is the change from baseline (Day 1) to week 12 in the 24-hour average SBP of the bexagliflozin group compared to the placebo group using a superiority testing at an overall two-sided 0.05 level of significance.

The primary endpoint of study 603B is the change from week 12 (cumulative week 24) to week 24 (cumulative week 36) in the 24-hour average SBP in the bexagliflozin group compared to the placebo group using a superiority testing at an overall two-sided 0.05 level of significance.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
* Study 603A: bexagliflozin tablets, 20 mg or placebo
* Study 603B week 1 to week 12: bexagliflozin tablets, 20 mg, open-labeled
* Study 603B week 13 to week 24: bexagliflozin tablets, 20 mg or placebo

Study Groups

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Sequence 1

Period 1: Placebo Period 2: Bexagliflozin Period 3: Bexagliflozin

Group Type OTHER

Bexagliflozin

Intervention Type DRUG

Bexagliflozin tablet, 20 mg

Placebo

Intervention Type DRUG

Placebo (inactive) tablet to match the active drug

Sequence 2

Period 1: Placebo Period 2: Bexagliflozin Period 3: Placebo

Group Type OTHER

Bexagliflozin

Intervention Type DRUG

Bexagliflozin tablet, 20 mg

Placebo

Intervention Type DRUG

Placebo (inactive) tablet to match the active drug

Sequence 3

Period 1: Bexagliflozin Period 2: Bexagliflozin Period 3: Bexagliflozin

Group Type OTHER

Bexagliflozin

Intervention Type DRUG

Bexagliflozin tablet, 20 mg

Sequence 4

Period 1: Bexagliflozin Period 2: Bexagliflozin Period 3: Placebo

Group Type OTHER

Bexagliflozin

Intervention Type DRUG

Bexagliflozin tablet, 20 mg

Placebo

Intervention Type DRUG

Placebo (inactive) tablet to match the active drug

Interventions

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Bexagliflozin

Bexagliflozin tablet, 20 mg

Intervention Type DRUG

Placebo

Placebo (inactive) tablet to match the active drug

Intervention Type DRUG

Other Intervention Names

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EGT0001442

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Theracos

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Allegretti, M.D.

Role: STUDY_DIRECTOR

Massachusetts General Hospital

Locations

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Clinical Research Site

Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Foley, Alabama, United States

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Gulf Shores, Alabama, United States

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Glendale, Arizona, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Bellflower, California, United States

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Fair Oaks, California, United States

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Fresno, California, United States

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Lincoln, California, United States

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Los Angeles, California, United States

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San Gabriel, California, United States

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Santa Rosa, California, United States

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Upland, California, United States

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Colorado Springs, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Golden, Colorado, United States

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Stamford, Connecticut, United States

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Decatur, Georgia, United States

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Decatur, Georgia, United States

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Lithonia, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Avon, Indiana, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Council Bluffs, Iowa, United States

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Prairie Village, Kansas, United States

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Lexington, Kentucky, United States

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Paducah, Kentucky, United States

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Versailles, Kentucky, United States

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New Orleans, Louisiana, United States

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Auburn, Maine, United States

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Silver Spring, Maryland, United States

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Edina, Minnesota, United States

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Bridgeton, Missouri, United States

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St Louis, Missouri, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Trenton, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Hartsdale, New York, United States

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The Bronx, New York, United States

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Shelby, North Carolina, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Dayton, Ohio, United States

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Dublin, Ohio, United States

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Grove City, Ohio, United States

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Lyndhurst, Ohio, United States

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Edmond, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Altoona, Pennsylvania, United States

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Hatboro, Pennsylvania, United States

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Lincoln, Rhode Island, United States

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Clinical Research Site 2

Anderson, South Carolina, United States

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Anderson, South Carolina, United States

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Greer, South Carolina, United States

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Kingsport, Tennessee, United States

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Knoxville, Tennessee, United States

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Arlington, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Kingwood, Texas, United States

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Mesquite, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Tomball, Texas, United States

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Layton, Utah, United States

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Murray, Utah, United States

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West Jordan, Utah, United States

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Arlington, Virginia, United States

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Burke, Virginia, United States

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Charlottesville, Virginia, United States

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Danville, Virginia, United States

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Manassas, Virginia, United States

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Tacoma, Washington, United States

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Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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THR-1442-C-603

Identifier Type: -

Identifier Source: org_study_id

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