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A study to assess whether relacorilant works and is safe to use in patients with Hypercortisolism due to Cortisol-Secreting Adrenal Adenomas or Hyperplasia; some patients will receive relacorilant whilst others receive a placebo.

Phase 1
Conditions
Hypercortisolism
MedDRA version: 22.1Level: LLTClassification code 10020611Term: HypercortisolismSystem Organ Class: 100000004860
Therapeutic area: Body processes [G] - Physiological processes [G07]
Registration Number
EUCTR2019-004956-12-RO
Lead Sponsor
Corcept Therapeutics Incorporated
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
130
Inclusion Criteria

To enroll in this study, each patient Each patient must meet the following key inclusion criteria:
1. Male or female, 18 to 80 years of age, inclusive.
2. Lack of cortisol suppression (>1.8 µg/dL serum cortisol with adequate dexamethasone levels) on either 1-mg overnight or 2-mg 48-hour DST during Screening.
3. Suppressed or low (=15 pg/mL) early-morning ACTH levels on at least 2 occasions during Screening.
4. A radiologically confirmed adrenal lesion (single adenoma, multiple adenomas, hyperplasia [=3 times the size of the normal adrenal gland]).
5. 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).
• Systolic hypertension (mean SBP =130 to =170 mm Hg) based on 24-hour ABPM.
6. If receiving medical treatment for DM/IGT or hypertension, they have been on a stable dose for at least 4 weeks prior to first dose of study medication.
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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 abnormal liver test results (total bilirubin >1.5×ULN or elevated alanine aminotransferase or aspartate aminotransferase >3×ULN at Baseline).
4. Has severe renal insufficiency (glomerular filtration rate =29 mL/min at Baseline).
5. Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
6. 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).
7. Has persistent atrial fibrillation.
8. Has used or plans to use any treatments for Cushing syndrome within 12 weeks prior to Screening and throughout the study, including mifepristone, metyrapone, ketoconazole, fluconazole, or any investigational drug for treatment of Cushing syndrome
9. Has adrenocortical carcinoma.
10. 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 to rule-in or rule-out this possibility.
11. Has autonomous cosecretion of aldosterone.
12. Has plans for adrenalectomy or nodulectomy during the study, including follow-up.
13. Has taken any non-Cushing syndrome investigational drug within 4 weeks prior to Baseline, or within less than 5 times the drug’s half-life, whichever is longer.
14. 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.
15. Ongoing use of any strong CYP3A inhibitor/inducer or any other prohibited medications.
16. Is pregnant or lactating.
17. Is a female patient of childbearing potential who cannot use a highly effective method of contraception (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).
18. Has an acute or unstable medical problem that could be aggravated by treatment with the investigational study drug.
19. Has a history of severe reaction to the study drug, to a similar class of drug, or to the study drug’s excipient.
20. In the Investigator’s opinion, should not participate in the study or may not be capable of following the study schedule.
21. Taking medication for treatment of HIV, hepatitis B, or hepatitis C infection.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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