Evidence map›Paper›PMID 39152532›Full record

Trial reportClinical and translational science2024

First-in-human study evaluating safety, pharmacokinetics, and pharmacodynamics of lorundrostat, a novel and highly selective aldosterone synthase inhibitor.

Hidetoshi Shimizu, Michael A Tortorici, Yoshiyasu Ohta, Kei Ogawa, Sheikh Mohammed Ashfaq Rahman, Aya Fujii, Yuki Hiraga, Mizue Kawai, Kanami Sugimoto-Kawabata, Mattheus Thijs van Iersel and 4 more

Abstract readRandomized Controlled TrialClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 8 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 8 syntheses or guidelines pooled it.

  1. Pooled it
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  4. Pooled it
  5. Efficacy and Safety of Lorundrostat in Uncontrolled and/or Treatment Resistant Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2025
    Pooled it
  6. Pooled it
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  9. Trial
  10. Trial
  11. Article
  12. Emerging Medical Therapies for Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2026
    Review
  13. Review
  14. Article
  15. Review
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  18. Review
  19. Optimal Dose of Lorundrostat in Uncontrolled Hypertension: A Dose Response Meta-Analysis.Dose-response : a publication of International Hormesis Society
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Hidetoshi ShimizuClinical Pharmacology Group, Data Science Department, Ikuyaku, Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.ORCID 0000-0002-4208-9790
Michael A TortoriciMineralys Therapeutics, Radnor, Pennsylvania, USA.
Yoshiyasu OhtaClinical Research & Development II, Ikuyaku, Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
Kei OgawaClinical Pharmacology Group, Data Science Department, Ikuyaku, Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
Sheikh Mohammed Ashfaq RahmanClinical Department, Mitsubishi Tanabe Pharma Corporation, London, UK.
Aya FujiiResearch Unit/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Kanagawa, Japan.
Yuki HiragaTranslational Research, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
Mizue KawaiResearch Unit/Immunology & Inflammation, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharm Corporation, Kanagawa, Japan.
Kanami Sugimoto-KawabataSohyaku Strategy & Planning Department, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
Mattheus Thijs van IerselICON, Groningen, The Netherlands.
Jan Jaap van LierICON, Groningen, The Netherlands.
Stephen DjedjosMineralys Therapeutics, Radnor, Pennsylvania, USA.
B T SlingsbyMineralys Therapeutics, Radnor, Pennsylvania, USA.
David M RodmanMineralys Therapeutics, Radnor, Pennsylvania, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of the mineralocorticoid hormone aldosterone is an increasingly prevalent cause of hypertension. Aldosterone synthase (CYP11B2) shares 93% homology to 11β-hydroxylase (CYP11B1), which produces cortisol. Lorundrostat, a highly selective inhibitor of CYP11B2, is a potential safe and effective treatment for aldosterone-dependent, uncontrolled hypertension, including treatment-resistant hypertension. Lorundrostat showed highly selective inhibition of CYP11B2 in vitro, with 374-fold selectivity for CYP11B2 vs. CYP11B1. A first-in-human study of single ascending doses ranging from 5 to 800 mg and multiple ascending doses ranging from 40 to 360 mg once daily was conducted in healthy participants. After single- and multiple-dose administration, lorundrostat plasma levels peaked 1-3 h after administration with a t

Indexed as

AldosteroneCytochrome P-450 CYP11B2Dose-Response Relationship, DrugAdolescentAdultDouble-Blind MethodEnzyme InhibitorsFemaleHealthy VolunteersHumansMaleMiddle AgedYoung AdultAldosteroneCytochrome P-450 CYP11B2Enzyme Inhibitors

Identifiers

PMID39152532
PMCPMC11329366

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.