Uncontrolled Hypertension, Resistant Hypertension
Conditions
Keywords
Hypertension, Uncontrolled hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase
Brief summary
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).
Interventions
DRUGBaxdrostat
Baxdrostat tablet administered orally, once daily (QD). Unit dose strengths: * 1 mg per tablet for 1 mg baxdrostat Arm; * 2 mg per tablet for 2 mg baxdrostat Arm.
DRUGPlacebo
Placebo tablet matching baxdrostat, administered orally, once daily (QD).
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in seated systolic blood pressure for 1 mg baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12 |
| Change from baseline in seated systolic blood pressure for 2 mg baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat versus placebo on seated systolic blood pressure at Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in seated SBP for 2 mg baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat vs placebo on seated SBP at Week 12 in the resistant hypertension (rHTN) subpopulation |
| Change from baseline in seated diastolic blood pressure (DBP) for 2 mg baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat vs placebo on seated diastolic blood pressure (DBP) at Week 12 |
| Achieving seated SBP < 130 mmHg for 2 mg baxdrostat | At Week 12 | To assess the effect of 2 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12 |
| Change from baseline in seated DBP for 1 mg baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat vs placebo on seated DBP at Week 12 |
| Achieving seated SBP < 130 mmHg for 1 mg baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat vs placebo on achieving seated SBP \< 130 mmHg at Week 12 |
| Change from baseline in seated SBP for 1 mg baxdrostat | At Week 12 | To assess the effect of 1 mg baxdrostat vs placebo on seated SBP at Week 12 in the rHTN subpopulation |
| Change from randomised withdrawal baseline (Week 24) in seated systolic blood pressure (SBP) for 2 mg baxdrostat | At Week 32 | To assess the effect of 2 mg baxdrostat vs placebo on seated systolic blood pressure (SBP) at 8 weeks after randomised withdrawal |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | Up to Week 54 | To assess the safety and tolerability of baxdrostat versus placebo. Occurrence of adverse events (AE), including serious adverse events (SAEs), adverse events leading to treatment discontinuation (DAE) and adverse events of special interest (AESI). |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Poland, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Outcome results
None listed