Resistant Hypertension
Conditions
Keywords
Hypertension, Resistant hypertension, Blood pressure, Baxdrostat, CIN-107, Aldosterone, Aldosterone synthase, Aldosterone synthase inhibitor
Brief summary
This is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg Baxdrostat vs. placebo, administered QD orally, on the reduction of SBP, measured by average 24-hour ABPM in 212 participants with rHTN (defined as seated SBP ≥ 140 mmHg at Screening and mean ambulatory SBP ≥ 130 mmHg at baseline, despite a stable regimen of ≥ 3 antihypertensive agents, one of which is a diuretic).
Detailed description
This is a Phase III, multicentre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and the effect of 2 mg baxdrostat versus placebo, administered once a day (QD) orally, on the reduction of ambulatory SBP in participants with rHTN, defined as BP targets not being achieved in an individual despite the use of at least 3 antihypertensive agents of different classes (at maximum tolerated dose in the judgement of the Investigator), one of which is a diuretic.
Interventions
DRUGBaxdrostat
Baxdrostat tablet administered orally, once daily (QD). Unit dose strength: • 2 mg per tablet.
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
* Participant must be ≥ 18 years old, at the time of signing the informed consent. * Mean seated SBP on AOBPM of ≥ 140 mmHg and \< 170 mmHg at Screening. * 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, for at least 4 weeks prior to screening. Beta blockers used to treat other conditions (ie, migraine, HF, coronary artery disease) should not be counted as an antihypertensive medication for the purpose of qualifying for this study. * Have eGFR ≥ 45 mL/min/1.73 m2 at Screening. * Serum potassium (K+) level ≥ 3.5 and \< 5.0 mmol/L at Screening, determined as per central laboratory * Randomization Criteria: mean ambulatory SBP of ≥ 130 mmHg at randomisation.
Exclusion criteria
* Mean seated SBP on AOBPM ≥ 170 mmHg. * Mean seated DBP on AOBPM ≥ 110 mmHg. * Serum sodium level \< 135 mmol/L at Screening, as per central laboratory. * Participant 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 HF class IV. * Persistent atrial fibrillation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in ambulatory 24-hour average SBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory 24-hour average SBP at Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in ambulatory night-time average SBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory night-time average SBP at Week 12. |
| Change from baseline in seated SBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on seated SBP at Week 12. |
| Participants achieving ambulatory 24-hour average SBP of < 130 mmHg | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on achieving ambulatory 24-hour average SBP \< 130 mmHg at Week 12. |
| Change from baseline in ambulatory 24-hour average DBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory 24-hour average DBP at Week 12. |
| Change from baseline in ambulatory night-time average DBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory night-time average DBP at Week 12. |
| Change from baseline in the average ambulatory daytime average DBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory daytime average DBP at Week 12. |
| Change from baseline on seated DBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on seated DBP at Week 12. |
| Change from baseline in ambulatory daytime average SBP | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo on ambulatory daytime average SBP at Week 12. |
| Participants achieving a nocturnal SBP dipping of ≥ 10% | At Week 12 | To assess the effect of treatment with baxdrostat 2 mg versus placebo in the nocturnal dipping pattern at Week 12. |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Czechia, Germany, Greece, Hungary, Malaysia, Philippines, Poland, Saudi Arabia, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Outcome results
None listed