Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study

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Abstract

Introduction/Purpose

Relacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS).

Materials and Methods

A single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%).

Results

35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred.

Conclusions

The SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.

Related collections

Most cited references 43

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Author and article information

Contributors

Rosario Pivonello: URI : https://loop.frontiersin.org/people/165673

Irina Bancos: URI : https://loop.frontiersin.org/people/937352

Richard A. Feelders: URI : https://loop.frontiersin.org/people/164628

Atil Y. Kargi: URI : https://loop.frontiersin.org/people/95743

Murray B. Gordon: URI : https://loop.frontiersin.org/people/1176226

Cary N. Mariash: URI : https://loop.frontiersin.org/people/1298913

Andreas G. Moraitis: URI : https://loop.frontiersin.org/people/1219639

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 14 July 2021

Publication date Collection: 2021

Volume: 12

Electronic Location Identifier: 662865

Affiliations

[1] ¹ Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli , Naples, Italy

[2] ² Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic , Rochester, MN, United States

[3] ³ Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center , Rotterdam, Netherlands

[4] ⁴ Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Miami , Miami, FL, United States

[5] ⁵ Department of Endocrinology, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Denver , Aurora, CO, United States

[6] ⁶ Allegheny Neuroendocrinology Center, Allegheny General Hospital , Pittsburgh, PA, United States

[7] ⁷ Methodist Research Institute, Indiana University School of Medicine , Indianapolis, IN, United States

[8] ⁸ Department of Clinical and Biological Sciences, Internal Medicine 1 – San Luigi Gonzaga Hospital, University of Turin , Orbassano, Italy

[9] ⁹ Biostatistics, Trialwise, Inc , Houston, TX, United States

[10] ¹⁰ Drug Research and Development, Corcept Therapeutics , Menlo Park, CA, United States

Author notes

Edited by: Corin Badiu, Carol Davila University of Medicine and Pharmacy, Romania

Reviewed by: Annamaria Anita Livia Colao, University of Naples Federico II, Italy; George Mastorakos, National and Kapodistrian University of Athens, Greece

*Correspondence: Andreas G. Moraitis, amoraitis@ 123456corcept.com

This article was submitted to Pituitary Endocrinology, a section of the journal Frontiers in Endocrinology

Article

DOI: 10.3389/fendo.2021.662865

PMC ID: 8317576

PubMed ID: 34335465

SO-VID: 85bf2c4a-45b5-456d-8a3a-798b81a02ecb

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 01 February 2021

Date accepted : 25 June 2021

Page count

Figures: 4, Tables: 5, Equations: 0, References: 43, Pages: 12, Words: 6996

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Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study

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Abstract

Introduction/Purpose

Materials and Methods

Results

Conclusions

Related collections

Journal of the ASEAN Federation of Endocrine Societies

Most cited references 43

2020 International Society of Hypertension Global Hypertension Practice Guidelines

Trail Making Test A and B: normative data stratified by age and education.

Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline.

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Cited by 18

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