Efficacy and safety of esaxerenone (CS-3150) for the treatment of essential hypertension: a phase 2 randomized, placebo-controlled, double-blind study

Sadayoshi Ito,Yasuyuki Okuda,Hiromi Rakugi,Satoru Yamakawa,Hiroshi Itoh

doi:10.1038/s41371-019-0207-x

Abstract

This was a phase 2, multicenter, randomized, double-blind, placebo-controlled, open-label comparator study to investigate the efficacy and safety of esaxerenone (CS-3150), a novel non-steroidal mineralocorticoid receptor blocker, in Japanese patients with essential hypertension. Eligible patients (n = 426) received esaxerenone (1.25, 2.5, or 5 mg/day), placebo, or eplerenone (50–100 mg/day) for 12 weeks. The primary efficacy endpoint was the change from baseline in sitting systolic and diastolic blood pressure (BP). Safety endpoints included adverse events and serum K+ elevation. There were significant dose–response reductions in the 2.5 and 5 mg/day esaxerenone groups for sitting BP (both p < 0.001) and 24-h BP (both p < 0.0001) compared with placebo, with a mean (95% confidence interval) change in sitting BP of −7.0 (−9.5 to −4.6)/−3.8 (−5.2 to −2.4) mmHg in the placebo group, and −10.7 (−13.2 to −8.2)/−5.0 (−6.4 to −3.6) mmHg, −14.3 (−16.8 to −11.9)/−7.6 (−9.1 to −6.2) mmHg, and −20.6 (−23.0 to −18.2)/ −10.4 (−11.8 to −9.0) mmHg for the 1.25, 2.5, and 5 mg/day esaxerenone groups, respectively, while the change was −17.4 (−19.9 to −15.0)/−8.5 (−9.9 to −7.1) mmHg for eplerenone. The incidence of adverse events was similar in all treatment groups. Serum K+ levels initially increased in proportion with esaxerenone dose but were stable from week 2 until week 12. Plasma esaxerenone concentration increased in proportion with the dose. In conclusion, esaxerenone is an effective and tolerable treatment option for patients with essential hypertension.

Highlights

Hypertension is a multifactorial disease involving complex interactions between various metabolic, neurohormonal, and Supplementary information The online version of this article contains supplementary material, which is available to authorized users.In addition to non-pharmacological treatments, management of hypertension often requires pharmacotherapy with an antihypertensive agent, which is a proven approach for reducing cardiovascular morbidity and mortality [4]
The adjusted LS geometric mean and corresponding 95% confidence intervals (CIs) were calculated for percentage change in each group at each time point using an analysis of covariance (ANCOVA) model, with change from baseline at each time point an objective variable, treatment group an explanatory variable, and screening period data
Summary statistics were calculated for determining the pharmacokinetics of plasma esaxerenone concentrations at each time point at weeks 4 and 12

Summary

Introduction

In addition to non-pharmacological treatments, management of hypertension often requires pharmacotherapy with an antihypertensive agent, which is a proven approach for reducing cardiovascular morbidity and mortality [4]. Monotherapy may be effective in some patients, failure to achieve the desired antihypertensive effect requires the concurrent use of multiple antihypertensive drugs as part of a multifactorial strategy [5, 6]. Many patients require three or more antihypertensive drugs to achieve a blood pressure (BP) level of

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