Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant

Phase 3

Completed

• Conditions: Cushing's syndrome; 10001353

• Registration Number: NL-OMON54706
• Lead Sponsor: Corcept Therapeutics Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

To enroll in the study, each patient must meet the following key inclusion
criteria: 1. Male or female, 18 to 80 years of age, inclusive 2. Has a
confirmed biochemical diagnosis of endogenous Cushing syndrome based on the
presence of at least 2 of the following: • UFC >= upper limit of normal (ULN) in
at least 2 complete 24-hour tests within the screening window • Late-night
salivary cortisol >= ULN in at least 2 tests (using a salivette) within the
screening window (Note: Test is not appropriate for night shift workers and
cannot be used to evaluate eligibility) • Lack of cortisol suppression (>=1.8 µg/
dL serum cortisol) on either 1-mg overnight or 2-mg 48-hour dexamethasone
suppression testing during Screening, or within 12 weeks before signing the
informed consent 3. Has at least 2 of the following clinical signs and symptoms
of Cushing syndrome: • Bodily characteristics of a Cushingoid appearance (e.g.,
facial rubor, moon facies, dorsocervical fat pad, supraclavicular fat pad) •
Increased body weight or central obesity • Proximal muscle weakness • Low bone
mass based on DXA scan • Psychiatric symptoms (including depression or
psychosis) • Skin manifestations: violaceous striae, acne, and/or hirsutism •
Easy bruisability 4. Has at least 1 of the following at Baseline: • DM (fasting
plasma glucose >=126 mg/dL and/or 2-hour oGTT plasma glucose >=200 mg/dL at 2
hours or HbA1c >= 6.5%) or IGT (plasma glucose >=140 mg/dL and <=200 mg/dL on a
2-hour oGTT glucose) (American Diabetes Association 2020) • Uncontrolled
hypertension (mean SBP >=135 to <=170 mm Hg and/or mean DBP >=85 to <=110 mm Hg)
based on 24-hour ABPM 5. If receiving medical treatment for DM/IGT or
hypertension, there has been no increase in medication dosage for at least 4
weeks prior to Baseline assessment. 6. If receiving medical treatment for
depression, there has been no increase in medication dosage for at least 6
weeks prior to Baseline 7. For women of childbearing potential, has a negative
serum pregnancy test at Screening and negative urine pregnancy test at Baseline

Exclusion Criteria

Patients who meet any of the following criteria will not be permitted entry to
the study: 1. Has severe, uncontrolled hypertension (mean SBP >=170 mm Hg or
mean DBP >=110 mm Hg at Screening), based on 24-hour ABPM 2. Has poorly
controlled DM (HbA1c >=12% at Screening) 3. Has a known *long term* history of
both hypertension and diabetes (defined as both hypertension and diabetes
diagnosed >=10 years prior to the initial diagnosis of endogenous CS) 4. Has a
history of cyclic Cushing*s syndrome with fluctuating clinical manifestations.
5. Has DM Type 1. 6. Has abnormal liver test results (total bilirubin >= 1.5×ULN
or elevated alanine aminotransferase or aspartate aminotransferase >=3×ULN at
Baseline) 7. Has severe renal insufficiency (glomerular filtration rate <=29
mL/min at Baseline) 8. Has uncontrolled, clinically significant hypothyroidism
or hyperthyroidism 9. Has prolonged QT interval corrected for heart rate using
Fridericia*s equation (QTcF) (>=450 ms for men and >=470 ms for women) with
normal QRS interval (<=120 ms) or QTcF interval >=500 ms with wide QRS interval
(>=120 ms) 10. Has received stereotactic radiation therapy for a Cushing
syndrome-related tumor within 24 months of Baseline or conventional pituitary
radiation therapy within 36 months of Baseline. 11. Has undergone pituitary
surgery <=3 months prior to Screening 12. Has used or plans to use any of the
following treatments for Cushing syndrome within 4 weeks prior to Baseline: -
Mifepristone - Adrenostatic medications: metyrapone, osilodrostat,
ketoconazole, fluconazole, aminoglutethimide, or etomidate - Serotonin
antagonists: cyproheptadine, ketanserin, or ritanserin - Dopamine agonists:
bromocriptine or cabergoline - Gamma-aminobutyric acid agonists: sodium
valproate - Short-acting somatostatin analogs: octreotide, lanreotide, or
pasireotide 13. Has used or plans to use somatostatin receptor ligands:
long-acting octreotide or pasireotide within 8 weeks prior to Baseline 14.
Patients who require inhaled glucocorticoid use and have no alternative option
if their condition deteriorates during the study. 15. Has adrenocortical
carcinoma 16. Has used mitotane prior to Baseline. 17. Has ectopic Cushing
syndrome and a life expectancy of <=3 years or receiving chemotherapy. 18. Has
pseudo-Cushing syndrome. Patients with known or suspected pseudo-Cushing
syndrome based on medical history (such as patients with severe obesity, major
depression, or a history of alcoholism) should undergo a dexamethasone-CRH
DDAVP stimulation test (Yanovski et al.1993, Giraldi et al. 2007, Yanovski et
al. 1998) to rule-in or rule-out this possibility 19. Has taken any
investigational drug within 4 weeks prior to Baseline, or within less than 5
times the drug*s half-life, whichever is longer 20. Ongoing use of
antidiabetic, antihypertensive, antidepressant or lipid-lowering medications
that are highly dependent on CYP3A for clearance and that cannot undergo dose
modification upon coadministration with strong CYP3A inhibitors 21. Ongoing use
of any strong CYP3A4 inducer or any other prohibited medications (Section
5.4.4) 22. Is pregnant or lactating 23. Is a female patient of childbearing
potential (including all women <=50 years old, women whose surgical
sterilization was performed <=6 months ago, and women who have had a m

Study & Design

• Study Type: Interventional
• Study Design: Not specified