Exposure-response analysis of the efficacy and safety of esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with or without diabetic kidney disease

Tomaschitz, 2010, Aldosterone and arterial hypertension, Nat Rev Endocrinol, 6, 83, 10.1038/nrendo.2009.263 Douglas, 1974, Treatment of low-renin essential hypertension. Comparison of spironolactone and a hydrochlorothiazide-triamterene combination, JAMA, 227, 518, 10.1001/jama.1974.03230180016005 Weinberger, 2002, Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension, Am J Hypertens, 15, 709, 10.1016/S0895-7061(02)02957-6 Lazich, 2014, Prediction and management of hyperkalemia across the spectrum of chronic kidney disease, Semin Nephrol, 34, 333, 10.1016/j.semnephrol.2014.04.008 2021 Kolkhof, 2015, Nonsteroidal antagonists of the mineralocorticoid receptor, Curr Opin Nephrol Hypertens, 24, 417, 10.1097/MNH.0000000000000147 Arai, 2015, Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist, Eur J Pharmacol, 761, 226, 10.1016/j.ejphar.2015.06.015 Ito, 2019, Efficacy and safety of esaxerenone (CS-3150) for the treatment of essential hypertension: a phase 2 randomized, placebo-controlled, double-blind study, J Hum Hypertens, 33, 542, 10.1038/s41371-019-0207-x Ito, 2020, Double-blind randomized phase 3 study comparing esaxerenone (CS-3150) and eplerenone in patients with essential hypertension (ESAX-HTN study), Hypertension, 75, 51, 10.1161/HYPERTENSIONAHA.119.13569 Ito, 2019, Efficacy and safety of esaxerenone (CS-3150) for the treatment of type 2 diabetes with microalbuminuria: a randomized, double-blind, placebo-controlled, phase II trial, Clin J Am Soc Nephrol, 14, 1161, 10.2215/CJN.14751218 Ito, 2020, Esaxerenone (CS-3150) in patients with type 2 diabetes and microalbuminuria (ESAX-DN): phase 3 randomized controlled clinical trial, Clin J Am Soc Nephrol, 15, 1715, 10.2215/CJN.06870520 Ito, 2021, Antihypertensive effects and safety of esaxerenone in patients with moderate kidney dysfunction, Hypertens Res, 44, 489, 10.1038/s41440-020-00585-y Itoh, 2019, Efficacy and safety of dosage-escalation of low-dosage esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes and albuminuria: a single-arm, open-label study, Hypertens Res, 42, 1572, 10.1038/s41440-019-0270-2 2022 Rakugi, 2021, Management of hyperkalemia during treatment with mineralocorticoid receptor blockers: findings from esaxerenone, Hypertens Res, 44, 371, 10.1038/s41440-020-00569-y Overgaard, 2015, Establishing good practices for exposure-response analysis of clinical endpoints in drug development, CPT Pharmacometrics Syst Pharmacol, 4, 565, 10.1002/psp4.12015 Yoshihara, 2023, Population pharmacokinetics of esaxerenone, a novel non-steroidal mineralocorticoid receptor blocker, in patients with essential hypertension, patients with diabetic nephropathy, and healthy volunteers, Drug Metabol Pharmacokinet Xu, 2018, Full covariate modelling approach in population pharmacokinetics: understanding the underlying hypothesis tests and implications of multiplicity, Br J Clin Pharmacol, 84, 1525, 10.1111/bcp.13577 Gillis, 2016, Sex differences in hypertension: recent advances, Hypertension, 68, 1322, 10.1161/HYPERTENSIONAHA.116.06602 Faulkner, 2020, Female sex, a major risk factor for salt-sensitive hypertension, Curr Hypertens Rep, 22, 99, 10.1007/s11906-020-01113-6 Shibata, 2012, Mineralocorticoid receptor-associated hypertension and its organ damage: clinical relevance for resistant hypertension, Am J Hypertens, 25, 514, 10.1038/ajh.2011.245 Gordon, 2005, Low renin hypertensive states: perspectives, unsolved problems, future research, Trends Endocrinol Metabol, 16, 108, 10.1016/j.tem.2005.02.004 Mahmud, 2005, Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone?, Am J Hypertens, 18, 1631, 10.1016/j.amjhyper.2005.06.010 Hunter, 2019, Hyperkalemia: pathophysiology, risk factors and consequences, Nephrol Dial Transplant, 34 Schnider, 2021, The drug titration paradox: correlation of more drug with less effect in clinical data, Clin Pharmacol Ther, 110, 401, 10.1002/cpt.2162 Pitt, 2008, Serum potassium and clinical outcomes in the eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS), Circulation, 118, 1643, 10.1161/CIRCULATIONAHA.108.778811 Zhu, 2021, The safety and efficacy of low-dose mineralocorticoid receptor antagonists in dialysis patients: a meta-analysis, Medicine (Baltim), 100, 10.1097/MD.0000000000024882