A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension

AstraZeneca796 enrolled

Overview

This is a Phase III, multicentre, randomised, double-blinded, placebo-controlled, parallel group study to evaluate the safety, tolerability and effect of 1 or 2 mg baxdrostat versus placebo, administered once daily (QD) orally, on the reduction of systolic blood pressure in approximately 720 participants aged ≥ 18 years with hypertension, despite a stable regimen of 2 antihypertensive agents at baseline, one of which is a diuretic (uncontrolled hypertension); or ≥ 3 antihypertensive agents at baseline, one of which is a diuretic (treatment-resistant hypertension).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

796

Conditions

Uncontrolled Hypertension Resistant Hypertension

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female participants must be ≥ 18 years old * Mean sitting systolic blood pressure on automated office blood pressure measurement ≥ 140 mmHg and \< 170 mmHg at Screening * Fulfil at least 1 of the following 2 criteria: 1. uHTN subpopulation: have a stable regimen of 2 antihypertensive medications, from different therapeutic classes (at least one must be a diuretic), at maximum tolerated dose in the judgement of the Investigator 2. rHTN subpopulation: have a stable regimen of ≥ 3 antihypertensive medications, from different therapeutic classes (at least one must be a diuretic), at maximum tolerated dose in the judgement of the Investigator * Estimated glomerular filtration rate ≥ 45 mL/min/1.73m2 at Screening * Serum potassium (K+) level ≥ 3.5 and \< 5.0 mmol/L at Screening * Randomisation Criterion: * Sitting systolic blood pressure on attended automated office blood pressure measurement of ≥ 135 mmHg at the Baseline Visit Exclusion Criteria: * Mean sitting systolic blood pressure on attended automated office blood pressure measurement ≥ 170 mmHg * Mean seated diastolic blood pressure on attended automated office blood pressure measurement ≥ 110 mmHg * Serum sodium level \< 135 mmol/L at Screening * Has the following known secondary causes of hypertension: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation * New York Heart Association functional heart failure class IV at Screening * Persistent atrial fibrillation

Locations (263)

Research Site

Saraland, Alabama, United States

Research Site

Scottsdale, Arizona, United States

Research Site

Sun City West, Arizona, United States

Research Site

Surprise, Arizona, United States

Research Site

Little Rock, Arkansas, United States

Research Site

Outcomes

Primary Outcomes

Change From Baseline in Seated Systolic Blood Pressure for 2 mg Baxdrostat

To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Change From Baseline in Seated Systolic Blood Pressure for 1 mg Baxdrostat

To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Secondary Outcomes

Change From Randomised Withdrawal Baseline (Week 24) in Seated Systolic Blood Pressure (SBP) for 2 mg Baxdrostat

To assess the effect of 2 mg baxdrostat vs placebo on seated systolic blood pressure (SBP) at 8 weeks after randomised withdrawal (RWD). All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 32

Change From Baseline in Seated SBP for 2 mg Baxdrostat in the Resistant Hypertension Subpopulation

To assess the effect of 2 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 2 mg Baxdrostat

To assess the effect of 2 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Number of Participants Who Achieved Seated SBP < 130 mmHg for 2 mg Baxdrostat

To assess the effect of 2 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Change From Baseline in Seated SBP for 1 mg Baxdrostat in the Resistant Hypertension Subpopulation

To assess the effect of 1 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 1 mg Baxdrostat

To assess the effect of 1 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12

Number of Participants Who Achieved Seated SBP < 130 mmHg for 1 mg Baxdrostat

To assess the effect of 1 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12. All available measurements were included, and missing data were multiply imputed.

Time frame: At Week 12