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

NCT03514641 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: THR-1442-C-603
• Study Type: interventional
• Target: 673
• Locations: 1 country
• Sites: 87

Brief Summary

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.

Conditions

Essential Hypertension

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• 603A, Reduction of Mean Ambulatory Systolic Blood Pressure

  Baseline (Day 1) to week 12

• 603A, 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

  Baseline (Day 1) to week 12

• 603A, 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

  Baseline (Day 1) to week 12

Other Outcomes (2)

• Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure

  Baseline (Day 1) to cumulative week 36

• Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure

  Baseline (Day 1) to cumulative week 36

Study Arms (4)

Sequence 1

OTHER

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

Drug: Bexagliflozin; Drug: Placebo

Sequence 2

OTHER

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

Drug: Bexagliflozin; Drug: Placebo

Sequence 3

OTHER

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

Drug: Bexagliflozin

Sequence 4

OTHER

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

Drug: Bexagliflozin; Drug: Placebo

Interventions

Bexagliflozin DRUG

Bexagliflozin tablet, 20 mg

Also known as: EGT0001442

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Placebo DRUG

Placebo (inactive) tablet to match the active drug

Sequence 1; Sequence 2; Sequence 4

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Theracos: lead

Study Sites (87)

Clinical Research Site

Birmingham, Alabama, 35205, United States

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Birmingham, Alabama, 35211, United States

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Birmingham, Alabama, 35242, United States

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Foley, Alabama, 36535, United States

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Gulf Shores, Alabama, 36542, United States

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Glendale, Arizona, 85306, United States

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Mesa, Arizona, 85206, United States

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Phoenix, Arizona, 85020, United States

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Tucson, Arizona, 85741, United States

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Anaheim, California, 92801, United States

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Bellflower, California, 90706, United States

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Fair Oaks, California, 95628, United States

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Fresno, California, 93702, United States

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Lincoln, California, 95648, United States

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Los Angeles, California, 90057, United States

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San Gabriel, California, 91776, United States

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Santa Rosa, California, 95405, United States

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Upland, California, 91786, United States

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Colorado Springs, Colorado, 80909, United States

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Colorado Springs, Colorado, 80918, United States

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Denver, Colorado, 80246, United States

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Golden, Colorado, 80401, United States

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Stamford, Connecticut, 06905, United States

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Decatur, Georgia, 30030, United States

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Decatur, Georgia, 30032, United States

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Lithonia, Georgia, 30058, United States

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Chicago, Illinois, 60602, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60616, United States

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Avon, Indiana, 46123, United States

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Evansville, Indiana, 47714, United States

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Indianapolis, Indiana, 46260, United States

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Council Bluffs, Iowa, 51503, United States

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Prairie Village, Kansas, 66208, United States

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Lexington, Kentucky, 40503, United States

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Paducah, Kentucky, 42003, United States

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Versailles, Kentucky, 40383, United States

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New Orleans, Louisiana, 70115, United States

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Auburn, Maine, 04210, United States

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Silver Spring, Maryland, 20910, United States

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Edina, Minnesota, 55435, United States

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Bridgeton, Missouri, 63044, United States

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St Louis, Missouri, 63141, United States

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Henderson, Nevada, 89074, United States

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Las Vegas, Nevada, 89128, United States

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Trenton, New Jersey, 08611, United States

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Albuquerque, New Mexico, 87102, United States

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Brooklyn, New York, 11230, United States

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Hartsdale, New York, 10530, United States

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The Bronx, New York, 10455, United States

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Shelby, North Carolina, 28150, United States

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Akron, Ohio, 44311, United States

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Cincinnati, Ohio, 45236, United States

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Cincinnati, Ohio, 45245, United States

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Columbus, Ohio, 43213, United States

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Dayton, Ohio, 45439, United States

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Dublin, Ohio, 43215, United States

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Grove City, Ohio, 43214, United States

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Lyndhurst, Ohio, 44124, United States

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Edmond, Oklahoma, 73034, United States

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Oklahoma City, Oklahoma, 73119, United States

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Portland, Oregon, 97239, United States

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Altoona, Pennsylvania, 16602, United States

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Hatboro, Pennsylvania, 19040, United States

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Lincoln, Rhode Island, 02865, United States

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Clinical Research Site 2

Anderson, South Carolina, 29621, United States

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Anderson, South Carolina, 29621, United States

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Greer, South Carolina, 29650, United States

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Kingsport, Tennessee, 37660, United States

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Knoxville, Tennessee, 37909, United States

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Arlington, Texas, 76014, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77070, United States

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Kingwood, Texas, 77339, United States

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Mesquite, Texas, 75143, United States

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Plano, Texas, 75093, United States

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San Antonio, Texas, 78229, United States

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Tomball, Texas, 77375, United States

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Layton, Utah, 84041, United States

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Murray, Utah, 84123, United States

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West Jordan, Utah, 84088, United States

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Arlington, Virginia, 22207, United States

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Burke, Virginia, 22015, United States

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Charlottesville, Virginia, 22911, United States

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Danville, Virginia, 24541, United States

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Manassas, Virginia, 20110, United States

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Clinical Research Site

Tacoma, Washington, 98405, United States

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MeSH Terms

Conditions

Essential Hypertension

Interventions

bexagliflozin

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Albert Collinson
• Organization: Theracos Sub, LLC

acollinson@theracos.com

(508) 688-4221

Study Officials

• Andrew Allegretti, M.D.

  Massachusetts General Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: * 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: May 2, 2018
• Study Start: October 18, 2017
• Primary Completion: November 30, 2018
• Study Completion: November 30, 2018
• Last Updated: September 21, 2021
• Results First Posted: September 21, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (87)