Hypercortisolism MedDRA version: 22.1 Level: LLT Classification code 10020611 Term: Hypercortisolism System Organ Class: 10014698 - Endocrine disorders
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
Other descriptive na
Sponsors
Corcept Therapeutics Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To enroll in this study, 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 benign adrenal lesion (single adenoma, multiple adenomas, hyperplasia [=3 times the size of the normal adrenal gland]) within 3 years prior to Screening. 5. Has at least 1 of the following at Baseline: • Diabetes mellitus (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 impaired glucose tolerance (IGT) (plasma glucose =140 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 (average SBP >170 mm Hg or average DBP >110 mm Hg at Screening), based on 24-hour ABPM. 2. Has poorly controlled DM (HbA1c >12% at Screening). 3. Has DM Type 1. 4. Has abnormal liver test results (total bilirubin >1.5×ULN or elevated alanine aminotransferase or aspartate aminotransferase >3×ULN at Baseline). 5. Has severe renal insufficiency (glomerular filtration rate =29 mL/min/1.73 m2 at Baseline). 6. Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism. 7. 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 (=120 ms). 8. Has persistent atrial fibrillation. 9. Has used or plans to use any treatments for Cushing syndrome within 12 weeks prior to Screening and throughout the study, including mifepristone, metyrapone, osilodrostat, ketoconazole, fluconazole, or any investigational drug for treatment of Cushing syndrome 10. Patients who require inhaled glucocorticoids and have no alternative option if their condition deteriorates during the study. 11. Has adrenocortical carcinoma. 12. 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. 13. Has a history of cyclic Cushing syndrome with fluctuating clinical manifestations. 14. Has autonomous cosecretion of aldosterone. 15. Has plans for adrenalectomy or nodulectomy during the study, including follow-up. 16. 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. 17. 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 co-administration with strong CYP3A inhibitors. 18. Ongoing use of any strong CYP3A4 inducer or any other prohibited medications. 19. Is pregnant or lactating. 20. 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). 21. Has an acute or unstable medical problem that could be aggravated by treatment with the investigational study drug. 22. Has a history of severe reaction to the study drug, to a similar class of drug, or to the study drug’s excipient. 23. In the Investigator’s opinion, should not participate in the study or may not be capable of following the study schedule. 24. Has known HIV, hepatitis B, or hepatitis C infection and is taking medication for treatment of HIV, hepatitis B, or hepatitis C infection. 25. Has used mitotane prior to Baseline.
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 cortisol excess-related comorbidities (e.g., body weight) 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 average 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): Endpoints for Hypertension 1. In patients with systolic hypertension at Baseline, mean change in average diastolic blood pressure (DBP) and HR (based on 24-hour ABPM). 2. In patients with systolic hypertension at Baseline, mean change in daytime average SBP, DBP, and HR (based on 24-hour ABPM). 3. In patients with systolic hypertension at Baseline, mean change in nighttime average SBP, DBP, and HR (based on 24-hour ABPM). 4. In patients with systolic hypertension at Baseline, proportion of patients with any dose increase in antihypertensive medications due to worsening hypertension. 5. In patients with systolic hypertension at Baseline, proportion of patients with a reduction in 24-hour average SBP by 5 mm Hg (based on 24-hour ABPM). 6. In patients with systolic hypertension at Baseline, proportion of patients with any dose decrease in antihypertensive medication due to improved blood pressure. 7. In patients with systolic hypertension at Baseline, proportion of patients with normalization of the average SBP (<130 mm Hg, based on 24-hour ABPM). Endpoints for Hyperglycemia 1. In patients with DM (HbA1c at Baseline =6.5%), the mean change in HbA1c. 2. In patients with DM/IGT (HbA1c at Baseline =5.7%), the mean change in HbA1c. 3. Proportion of patients with HbA1c =6.5% at Baseline who achieved HbA1c <6.5%. 4. In patients with DM at Baseline, proportion of patients who achieved 2-hour oGTT glucose <140 mg/dL. 5. In patients with IGT at Baseline, proportion of patients who achieved 2-hour oGTT glucose <140 mg/dL. 6. In patients with DM/IGT at Baseline, proportion of patients with any dose decrease of diabetes medication due to improved glucose control. 7. In patients with DM/IGT at Baseline, proportion of patients with any dose increase of diabetes medications due to worsening hyperglycemia. Other Secondary Endpoint 1. In all patients, the mean change in body weight and waist circumference.;Timepoint(s) of evaluation of this end point: • Physi | — |
Countries
Austria, Bulgaria, Germany, Israel, Italy, Poland, Romania, Spain, United States
Contacts
Public ContactClinical Operations
Corcept Therapeutics Incorporated
Outcome results
None listed