Uncontrolled Hypertension, Resistant Hypertension
Conditions
Keywords
Hypertension, Uncontrolled hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase
Brief summary
The purpose of this study is to measure the efficacy and safety of baxdrostat in participants with uHTN or rHTN. The main objective is to compare the difference in SBP change from baseline at Week 12 of treatment between participants receiving 2 mg baxdrostat or 1 mg baxdrostat tablets and participants receiving placebo tablets.
Detailed description
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 QD orally, on the reduction of SBP in approximately 300 participants aged ≥ 18 years with HTN (≥ 140 mmHg at Screening; ≥ 135 mmHg at randomisation) despite a stable regimen of 2 antihypertensive agents at baseline, one of which is a diuretic (uHTN); or ≥ 3 antihypertensive agents at baseline, one of which is a diuretic (rHTN).
Interventions
DRUGBaxdrostat
Baxdrostat tablet administered orally, once daily (QD). Unit dose strength: * 1 mg per tablet for 1mg baxdrostat Arm * 2 mg per tablet for 2mg baxdrostat Arm
DRUGPlacebo
Placebo tablet administered orally, once daily (QD).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
placebo control
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants must be ≥ 18 years old. * Mean seated SBP on automated office blood pressure measurement (AOBPM) ≥ 140 mmHg at Screening. * Fulfil at least 1 of the following 2 criteria: 1. uHTN subpopulation: have a stable regimen (≥ 4 weeks) 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 (≥ 4 weeks) 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.• Mean seated SBP on AOBPM ≥ 135 mmHg at Baseline.
Exclusion criteria
* Mean seated SBP on AOBPM ≥ 170 mmHg. * Mean seated DBP on AOBPM ≥ 105 mmHg. * Serum sodium level (Na+) \< 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. * NYHA functional heart failure class IV at Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in seated SBP at Week 12 | At Week 12 | To assess the effect of 2 mg baxdrostat versus placebo on seated SBP at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in seated SBP at Week 12 | At Week 12 | To assess the effect of 1 mg baxdrostat versus placebo on seated SBP at Week 12 |
| Change from RWD baseline (Week 24) in seated SBP at Week 32 | At Week 32 | To assess the effect of 2 mg baxdrostat versus placebo on seated SBP at 8 weeks after randomised withdrawal |
| Change from baseline in the mean ambulatory 24-hour SBP at Week 12 as measured by ABPM | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg vs placebo on ambulatory 24-hour average SBP at Week 12 |
| Change from baseline in seated DBP at Week 12 | At Week 12 | To assess the effect of 2 mg baxdrostat versus placebo on seated DBP at Week 12 |
| Achieving seated SBP < 140 mmHg at Week 12 | At Week 12 | To assess the effect of 2 mg baxdrostat versus placebo on achieving seated SBP \< 140 mmHg at Week 12 |
Countries
Argentina, Australia, China, Hong Kong, India, Japan, Philippines, Russia, South Korea, Turkey (Türkiye), Vietnam
Outcome results
None listed