Primary Hyperaldosteronism
Conditions
Keywords
Primary hyperaldosteronism, Primary aldosteronism, PA, Baxdrostat, CIN-107, Aldosterone
Brief summary
This is a Phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, and efficacy of baxdrostat versus placebo, on the reduction of Seated Blood Pressure (SBP) and achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) in approximately 250 participants ≥ 18 years of age with Primary Aldosteronism (PA), with or without prior treatment with Mineralocorticoid Receptor Antagonists (MRAs) or potassium-sparing diuretics. Baxdrostat (or placebo) will be administered once daily, up-titrated after 2 weeks based on clinical response and tolerability. The study is planned to be conducted globally in approximately 90 study centres and 12 countries.
Interventions
DRUGBaxdrostat
Baxdrostat tablet administered orally, once daily (QD).
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants must be ≥ 18 years of age * Participants with a documented diagnosis of PA that fulfils the criteria defined in the 2016 or 2025 Endocrine Society Guidelines. * Participants willing and able to cease dosing of MRA or potassium sparing diuretics per study requirement for participants taking an MRA or potassium sparing diuretic at Screening. * eGFR ≥ 45 mL/min/1.73m2 at Screening * Serum potassium level ≥ 3.0 and \< 5.0 mmol/L at Screening determined as per the central laboratory. * Have a stable regimen of antihypertensive medications for at least 4 weeks prior to randomisation * Mean seated SBP on AOBPM of ≥ 135 mmHg and ≤ 170 mmHg and mean DBP of ≤ 105 mmHg. * Serum potassium (local lab) \> 3.0 mmol/L at randomization.
Exclusion criteria
\- If not taking an MRA or potassium sparing diuretic at Screening: Mean seated SBP \> 170 mmHg or mean seated DBP \>105 mmHg (on AOBPM). If taking an MRA or potassium sparing diuretic at Screening: Mean seated SBP \> 160 mmHg or mean seated DBP ≥ 100 mmHg. * Previous surgical intervention for an adrenal adenoma or have a planned adrenalectomy, renal nerve denervation, or adrenal ablative procedure during the course of the study. * Has the following known secondary causes of HTN: renal artery stenosis, uncontrolled or untreated hyperthyroidism, uncontrolled or untreated hypothyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation. * Serum sodium level \< 135 mmol/L at Screening, determined as per central laboratory. * New York Heart Association functional HF class IV at Screening. * Persistent atrial fibrillation. * Treatment with any MRA or potassium-sparing diuretic within 2 weeks prior to Randomisation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in seated Systolic Blood Pressure (SBP) at Week 8 | At week 8 | To assess the effect of baxdrostat versus placebo on seated Systolic Blood Pressure (SBP) at Week 8 |
| Achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) at week 8. | At week 8 | To assess the effect of baxdrostat vs placebo on achieving normalization of renin at week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from RWD baseline (Week 44) in Direct Renin Concentration (DRC) at Week 52 | At week 52 | To assess the effect of baxdrostat versus placebo on the percent change in DRC 8 weeks after the start of RWD |
| Change from Randomised withdrawal (RWD) baseline (Week 44) in seated Systolic Blood Pressure (SBP) at Week 52 | At week 52 | To assess the effect of baxdrostat versus placebo on seated Systolic Blood Pressure (SBP) 8 weeks after the start of Randomised withdrawal (RWD) |
| Achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) at week 8. | At week 8 | To assess the effect of baxdrostat vs placebo on achieving normalization of renin at week 8, in participants with dysregulated RAAS at baseline. |
| Achieving serum potassium ≥ 3.7 mmol/L without potassium supplementation at Week 8 in participants with serum potassium < 3.7 mmol/L or potassium supplementation at baseline | At week 8 | To assess the effect of baxdrostat versus placebo on achieving serum potassium ≥ 3.7 mmol/L without potassium supplementation at Week 8 in participants with serum potassium \< 3.7 mmol/L or potassium supplementation at baseline |
| Achieving 24-hour urine aldosterone < 10 μg at Week 8 in participants with 24-hour urine aldosterone ≥ 10 μg at baseline | At week 8 | To assess the effect of baxdrostat versus placebo on achieving 24-hour urine aldosterone \< 10 μg at Week 8 in participants with 24-hour urine aldosterone ≥ 10 μg at baseline |
| Percent change from baseline in 24-hour urine albumin at Week 8 | At week 8 | To assess the effect of baxdrostat versus placebo on 24-hour urine albumin at Week 8 |
Countries
Australia, Canada, China, France, Germany, India, Italy, Japan, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed