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

Essential Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03514641
• Other study ID #: THR-1442-C-603
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 18, 2017
• Est. completion date: November 30, 2018

Study information

• Verified date: August 2021
• Source: Theracos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 673
• Est. completion date: November 30, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Bexagliflozin
Bexagliflozin tablet, 20 mg
• Placebo
Placebo (inactive) tablet to match the active drug

Locations

Country	Name	City	State
United States	Clinical Research Site	Akron	Ohio
United States	Clinical Research Site	Albuquerque	New Mexico
United States	Clinical Research Site	Altoona	Pennsylvania
United States	Clinical Research Site	Anaheim	California
United States	Clinical Research Site	Anderson	South Carolina
United States	Clinical Research Site 2	Anderson	South Carolina
United States	Clinical Research Site	Arlington	Virginia
United States	Clinical Research Site	Arlington	Texas
United States	Clinical Research Site	Auburn	Maine
United States	Clinical Research Site	Avon	Indiana
United States	Clinical Research Site	Bellflower	California
United States	Clinical Research Site	Birmingham	Alabama
United States	Clinical Research Site	Birmingham	Alabama
United States	Clinical Research Site	Birmingham	Alabama
United States	Clinical Research Site	Bridgeton	Missouri
United States	Clinical Research Site	Bronx	New York
United States	Clinical Research Site	Brooklyn	New York
United States	Clinical Research Site	Burke	Virginia
United States	Clinical Research Site	Charlottesville	Virginia
United States	Clinical Research Site	Chicago	Illinois
United States	Clinical Research Site	Chicago	Illinois
United States	Clinical Research Site	Chicago	Illinois
United States	Clinical Research Site	Cincinnati	Ohio
United States	Clinical Research Site	Cincinnati	Ohio
United States	Clinical Research Site	Colorado Springs	Colorado
United States	Clinical Research Site	Colorado Springs	Colorado
United States	Clinical Research Site	Columbus	Ohio
United States	Clinical Research Site	Council Bluffs	Iowa
United States	Clinical Research Site	Dallas	Texas
United States	Clinical Research Site	Danville	Virginia
United States	Clinical Research Site	Dayton	Ohio
United States	Clinical Research Site	Decatur	Georgia
United States	Clinical Research Site	Decatur	Georgia
United States	Clinical Research Site	Denver	Colorado
United States	Clinical Research Site	Dublin	Ohio
United States	Clinical Research Site	Edina	Minnesota
United States	Clinical Research Site	Edmond	Oklahoma
United States	Clinical Research Site	Evansville	Indiana
United States	Clinical Research Site	Fair Oaks	California
United States	Clinical Research Site	Foley	Alabama
United States	Clinical Research Site	Fresno	California
United States	Clinical Research Site	Glendale	Arizona
United States	Clinical Research Site	Golden	Colorado
United States	Clinical Research Site	Greer	South Carolina
United States	Clinical Research Site	Grove City	Ohio
United States	Clinical Research Site	Gulf Shores	Alabama
United States	Clinical Research Site	Hartsdale	New York
United States	Clinical Research Site	Hatboro	Pennsylvania
United States	Clinical Research Site	Henderson	Nevada
United States	Clinical Research Site	Houston	Texas
United States	Clinical Research Site	Indianapolis	Indiana
United States	Clinical Research Site	Kingsport	Tennessee
United States	Clinical Research Site	Kingwood	Texas
United States	Clinical Research Site	Knoxville	Tennessee
United States	Clinical Research Site	Las Vegas	Nevada
United States	Clinical Research Site	Layton	Utah
United States	Clinical Research Site	Lexington	Kentucky
United States	Clinical Research Site	Lincoln	California
United States	Clinical Research Site	Lincoln	Rhode Island
United States	Clinical Research Site	Lithonia	Georgia
United States	Clinical Research Site	Los Angeles	California
United States	Clinical Research Site	Lyndhurst	Ohio
United States	Clinical Research Site	Manassas	Virginia
United States	Clinical Research Site	Mesa	Arizona
United States	Clinical Research Site	Mesquite	Texas
United States	Clinical Research Site	Murray	Utah
United States	Clinical Research Site	New Orleans	Louisiana
United States	Clinical Research Site	Oklahoma City	Oklahoma
United States	Clinical Research Site	Paducah	Kentucky
United States	Clinical Research Site	Phoenix	Arizona
United States	Clinical Research Site	Plano	Texas
United States	Clinical Research Site	Portland	Oregon
United States	Clinical Research Site	Prairie Village	Kansas
United States	Clinical Research Site	Saint Louis	Missouri
United States	Clinical Research Site	San Antonio	Texas
United States	Clinical Research Site	San Gabriel	California
United States	Clinical Research Site	Santa Rosa	California
United States	Clinical Research Site	Shelby	North Carolina
United States	Clinical Research Site	Silver Spring	Maryland
United States	Clinical Research Site	Stamford	Connecticut
United States	Clinical Research Site	Tacoma	Washington
United States	Clinical Research Site	Tomball	Texas
United States	Clinical Research Site	Trenton	New Jersey
United States	Clinical Research Site	Tucson	Arizona
United States	Clinical Research Site	Upland	California
United States	Clinical Research Site	Versailles	Kentucky
United States	Clinical Research Site	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	603A, Change in Seated Office Systolic Blood Pressure	Placebo-adjusted change in seated office systolic blood pressure	Baseline (Day 1) to week 12
Secondary	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
Secondary	603A, Change in Mean Ambulatory Diastolic Blood Pressure	Placebo-adjusted change in mean ambulatory diastolic blood pressure	Baseline (Day 1) to week 12
Secondary	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
Secondary	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
Secondary	603A, Change in Seated Office Diastolic Blood Pressure	Placebo-adjusted change in seated office diastolic blood pressure	Baseline (Day 1) to week 12
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)