A study to assess whether a product called relacorilant works and is safe to use in patients with Cushing Syndrome; some patients will receive relacorilant whilst others receive a placebo.

Phase 1

• Conditions: Endogenous Cushing syndrome; MedDRA version: 24.0Level: LLTClassification code 10011657Term: Cushings syndromeSystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Body processes [G] - Physiological processes [G07]

• Registration Number: EUCTR2018-003096-35-PL
• Lead Sponsor: Corcept Therapeutics Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-12
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 162

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 nigth 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)
• 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 146
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

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 mg 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 syndromerelated 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-CRHDDAVP stimulation test to rule-in or ruleout 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.
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 menstrual period in the last 2 years) who cannot use a highly effective method of contraception.
24. Has an acute or unstable medical problem that could be aggravated by treatment with the investigational study drug.
25. Has a history of hypersensitivity or severe reaction to

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified