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

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