Introduction
adverse renal events, hypertension, fibrosis, hypokalemia
FLUID RETENTION, INFLAMMATION, RENAL FAILURE, FIBROSIS, END ORGAN DAMAGE, ZONA, EVENTS, HYPERTENSION, CORTEX, VENTRICULAR HYPERTROPHY
Aldosterone is a key component of the renin-angiotensin-aldosterone system (RAAS). It is produced in the zona glomerulosa of the adrenal cortex in response to angiotensin II, high extracellular potassium concentration, and adrenocorticotropic hormone (ACTH). Aldosterone is involved in the regulation of fluid and electrolyte homeostasis via activation of the mineralocorticoid receptor (MR) on various tissues, which causes vasoconstriction of vascular smooth muscle and increased water and sodium absorption by the kidneys. The rate-limiting enzyme in the synthetic pathway of aldosterone is aldosterone synthase (also known as CYB11B2).Current first-line treatments for hypertension include diuretics, angiotensin-converting enzyme (ACE) inhibitors, and/or angiotensin receptor blockers (ARBs) [Chronically elevated aldosterone levels can lead to hypokalemia, sodium reabsorption, and fluid retention, resulting in increased blood pressure (BP). Furthermore, inflammation, end organ damage, fibrosis, cardiovascular events (e.g., ventricular hypertrophy), and adverse renal events (e.g., increased urinary albumin excretion, progression of renal failure) can occur with increased aldosterone levels independently of BP [Baxdrostat (CIN-107) is a highly potent, selective, and competitive small molecule inhibitor of aldosterone synthase, as demonstrated by preclinical and first-in-human clinical studies [In accordance with the in vitro and in vivo studies, baxdrostat demonstrated selectivity for aldosterone synthase as shown by a dose-dependent reduction in plasma aldosterone with no effect on ACTH-stimulated plasma cortisol levels following administration of single ascending doses in the first-in-human study [The favorable preclinical and early-phase clinical profiles of baxdrostat warranted assessment at steady state to confirm whether the effects are maintained following multiple doses [These results support the importance of the current multiple ascending dose assessment to further the understanding of baxdrostat attained with the prior single-dose study [