Double-Blind Randomized Phase 3 Study Comparing Esaxerenone (CS-3150) and Eplerenone in Patients With Essential Hypertension (ESAX-HTN Study)

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

Research output: Contribution to journalArticle

Abstract

Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events. This phase 3 multicenter, randomized, double-blind study compared the efficacy and safety of esaxerenone, a new selective nonsteroidal MR blocker, at 2.5 and 5 mg/day and eplerenone 50 mg/day in Japanese patients with essential hypertension. After a 4-week washout period, 1001 eligible adults with hypertension were randomized evenly to esaxerenone 2.5 or 5 mg/day or eplerenone 50 mg/day treatments, taken orally once daily for 12 weeks. Primary end points were changes in sitting systolic or diastolic blood pressure (BP) from baseline at the end of treatment. Esaxerenone 2.5 mg/day was noninferior to eplerenone for reductions in sitting and 24-hour BP. Reductions in BP with esaxerenone 5 mg/day were significantly greater than those with esaxerenone 2.5 mg/day. Changes in diurnal BP showed persistent 24-hour antihypertensive effects in all treatment groups. The proportions of patients achieving target sitting BP (<140/90 mm Hg) were 31.5%, 41.2%, and 27.5% with esaxerenone 2.5 and 5 mg/day and eplerenone 50 mg/day, respectively. Incidences of adverse events (all mild or moderate) were similar across treatment groups. These results indicate that esaxerenone is an effective and well-tolerated MR blocker in Japanese patients with essential hypertension, with BP-lowering activity at least equivalent to eplerenone. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT02890173.

Original languageEnglish
Pages (from-to)51-58
Number of pages8
JournalHypertension (Dallas, Tex. : 1979)
Volume75
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1

Fingerprint

Mineralocorticoid Receptors
Blood Pressure
Hypertension
Therapeutics
Essential Hypertension
CS-3150
eplerenone
Double-Blind Method
Antihypertensive Agents
Salts
Clinical Trials
Pathology
Safety
Incidence

Keywords

  • adult
  • blood pressure
  • eplerenone
  • esaxerenone
  • essential hypertension

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Double-Blind Randomized Phase 3 Study Comparing Esaxerenone (CS-3150) and Eplerenone in Patients With Essential Hypertension (ESAX-HTN Study). / Ito, Sadayoshi; Itoh, Hiroshi; Rakugi, Hiromi; Okuda, Yasuyuki; Yoshimura, Motonobu; Yamakawa, Satoru.

In: Hypertension (Dallas, Tex. : 1979), Vol. 75, No. 1, 01.01.2020, p. 51-58.

Research output: Contribution to journalArticle

Ito, Sadayoshi ; Itoh, Hiroshi ; Rakugi, Hiromi ; Okuda, Yasuyuki ; Yoshimura, Motonobu ; Yamakawa, Satoru. / Double-Blind Randomized Phase 3 Study Comparing Esaxerenone (CS-3150) and Eplerenone in Patients With Essential Hypertension (ESAX-HTN Study). In: Hypertension (Dallas, Tex. : 1979). 2020 ; Vol. 75, No. 1. pp. 51-58.
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abstract = "Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events. This phase 3 multicenter, randomized, double-blind study compared the efficacy and safety of esaxerenone, a new selective nonsteroidal MR blocker, at 2.5 and 5 mg/day and eplerenone 50 mg/day in Japanese patients with essential hypertension. After a 4-week washout period, 1001 eligible adults with hypertension were randomized evenly to esaxerenone 2.5 or 5 mg/day or eplerenone 50 mg/day treatments, taken orally once daily for 12 weeks. Primary end points were changes in sitting systolic or diastolic blood pressure (BP) from baseline at the end of treatment. Esaxerenone 2.5 mg/day was noninferior to eplerenone for reductions in sitting and 24-hour BP. Reductions in BP with esaxerenone 5 mg/day were significantly greater than those with esaxerenone 2.5 mg/day. Changes in diurnal BP showed persistent 24-hour antihypertensive effects in all treatment groups. The proportions of patients achieving target sitting BP (<140/90 mm Hg) were 31.5{\%}, 41.2{\%}, and 27.5{\%} with esaxerenone 2.5 and 5 mg/day and eplerenone 50 mg/day, respectively. Incidences of adverse events (all mild or moderate) were similar across treatment groups. These results indicate that esaxerenone is an effective and well-tolerated MR blocker in Japanese patients with essential hypertension, with BP-lowering activity at least equivalent to eplerenone. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT02890173.",
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