hypercortisolism MedDRA version: 22.1 Level: LLT Classification code 10020611 Term: Hypercortisolism System Organ Class: 100000004860
Conditions
Interventions
Product Name: Relacorilant
Product Code: [CORT125134]
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Relacorilant
CAS Number: 1496510-51-0
Current Sponsor code: CORT125134
Concentration unit:
Sponsors
CORCEPT THERAPEUTICS
Eligibility
Sex/Gender
All
Inclusion criteria
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 greater than or equal to126 mg/dL and/or 2-hour oGTT plasma glucose greater than or equal to 200 mg/dL at 2 hours, or HbA1c greater than or equal to 6.5%), or IGT (plasma glucose greater than or equal to140 mg/dL and =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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 greater than or equal to 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 (500 ms with wide QRS interval (greater than or equal to 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy of relacorilant for the treatment of hypercortisolism in patients with cortisol-secreting adrenal adenomas or hyperplasia, based on glycemic and blood pressure (BP) control at Week 22 compared with placebo • To assess the safety of relacorilant for the treatment of hypercortisolism;Secondary Objective: • To assess changes in the HPA axis, and cortisol excess-related comorbidities (body weight, dyslipidemia, and quality of life) in patients with hypercortisolism due to cortisol-secreting adrenal adenomas/hyperplasia • To assess the pharmacokinetics of relacorilant in patients with hypercortisolism due to cortisol secreting adrenal adenomas/hyperplasia;Primary end point(s): In patients with DM/IGT, the mean change in AUC glucose, from Baseline to Week 22 as compared between relacorilant and placebo arms. In patients with systolic hypertension, the mean change in mean systolic blood pressure (SBP) based on 24-hour ambulatory blood pressure monitoring (ABPM), from Baseline to Week 22 as compared between relacorilant and placebo arms. In all patients, assessment of safety based on treatment-emergent adverse events (TEAEs).;Timepoint(s) of evaluation of this end point: • DM/IGT mean change in AUC glucose: from baseline to week 22 (every 4 weeks). •AE screening: every 4 weeks from week 2 • ABPM (24-hour) test: Screening, every 4 weeks and at early termination | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Continuous Endpoints 1. In all patients, the mean change in ACTH levels. 2. In patients with DM (HbA1c at Baseline greater than or equal to 6.5%), the mean change in HbA1c. 3. In patients with DM (HbA1c at Baseline greater than or equal to 6.5%), the mean change in fasting glucose. 4. In patients with systolic hypertension, the mean change in nighttime SBP. 5. In patients with systolic hypertension, the mean change in DBP. 6. In all patients, the mean change in body weight and waist circumference. 7. In all patients, the mean change in total cholesterol, LDL cholesterol, triglycerides, and VLDL. 8. In patients with greater than or equal to 1 abnormal coagulation marker at Baseline, the mean change in factor VIII, von Willebrand factor, protein S, protein C, thrombin antithrombin (TAT), platelets, and partial thromboplastin time (PTT). 9. In all patients, the mean change in DHEA-S levels. 10. In all patients, the mean change in Cushing Quality-of-Life (Cushing QoL) score. Summarized with Proportions 1. Proportion of patients with IGT at Baseline who achieved 2-hour oGTT glucose 7 at Week 22/ET. 3. Proportion of patients with DM (HbA1c greater than or equal to 6.5) at Baseline who achieved 2-hour oGTT glucose <140 mg/dL at Week 22/ET. 4. For patients in the DM/IGT subgroup, the proportion of patients with any decrease in dose of diabetes medication. 5. Proportion of patients with a reduction in the mean change in SBP by greater than or equal to 5 mm Hg (based on 24-hour ABPM), from Baseline to Week 22/ET. 6. Proportion of patients with a reduction in the mean change in DBP by 5 mm Hg (based on 24-hour ABPM), from Baseline to Week 22/ET. 7. For patients in the systolic hypertension subgroup, the proportion of patients with any decrease in antihypertensive medication due to improved blood pressure. 8. Proportion of patients with normalization of the mean SBP (<130 mm Hg, based on 24-hour ABPM), from Baseline to Week 22/ET.;Timepoint(s) of | — |
Countries
Austria, Bulgaria, Germany, Israel, Italy, Poland, Romania, Spain, United States
Contacts
Public ContactClinical Operations
Corcept Therapeutics
Outcome results
None listed