Endogenous Cushing syndrome MedDRA version: 24.0 Level: LLT Classification code 10011657 Term: Cushings syndrome 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
Other descriptive name: (R)-(1-(4-FLUOROPHENYL)-6-((1-
Sponsors
Corcept Therapeutics Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 16
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 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 (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-CRHDDAVP stimulation test 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 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 o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy of relacorilant for the treatment of endogenous Cushing syndrome based on BP control at Week 12 of the Randomized-Withdrawal (RW) phase compared with placebo • To assess the safety of relacorilant for the treatment of endogenous Cushing syndrome ;Secondary Objective: • To assess changes in cortisol excess-related comorbidities (including DM/IGT and body weight) in patients with endogenous Cushing syndrome treated with relacorilant over the RW phase;Primary end point(s): The primary efficacy endpoint will be assessed in the RW phase. The study will be considered to have a positive outcome if the primary efficacy endpoint reaches statistical significance: • In patients with hypertension, the proportion of patients with a loss of response with respect to hypertension from Visit OL22 to RW12 based on 24-hour ABPM as compared between relacorilant and placebo arms, where loss of response is defined as follows: - In patients who met only the SBP response criterion, an increase in SBP =5 mm Hg. - In patients who met only the DBP response criterion, an increase in DBP by =5 mm Hg. - In patients who met both the SBP and DPB response criteria, an increase in either SBP or DBP by =5 mm Hg. - Any increase or modification in antihypertensive medication due to worsening hypertension. - Patients discontinue treatment in RW phase for any reason. • In all patients, assessment of safety based on treatment-emergent adverse events (TEAEs).;Timepoint(s) of evaluation of this end point: •AE: screening, baseline, every 4 weeks •ABPM: OL22, every 4 weeks in the RW phase •Concomitant medication, OL22, every 4 weeks in the RW phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints in the Randomized-Withdrawal Phase • Mean change from Visit OL22 to RW12 in 24-hour average SBP as compared between relacorilant and placebo. • Mean change from Visit OL22 to RW12 in 24-hour average DBP as compared between relacorilant and placebo. • Mean change from Visit OL22 to RW12 in body weight as compared between relacorilant and placebo. • In patients with DM/IGT, the mean change in AUCglucose from Visit OL22 to RW12 as compared between relacorilant and placebo arms. • For patients in the DM/IGT subgroup with response at OL22, the proportion of patients with a loss of response with respect to hyperglycemic control from Visit OL22 to RW12, as compared between relacorilant and placebo arms, where loss of response is defined as follows: In patients with DM: – Use of rescue medication (initiation or increase in diabetes medication due to worsening of hyperglycemic control), treatment discontinuation for any reason in RW phase, or loss to follow-up, OR – HbA1c has increased by =0.3% at Visit RW12 (compared to OL22), OR – The 2-hour time point of the plasma 2-hours oGTT glucose test at Visit RW12 is abnormal (=140 mg/dL) and has increased by at least 50% of the reduction observed between Baseline and Visit OL22. In patients with IGT: – Use of rescue medication (initiation or increase in diabetes medication due to worsening of hyperglycemic control), treatment discontinuation for any reason in RW phase, or loss to follow-up, OR – The 2-hour time point of the plasma 2-hour oGTT glucose test at Visit RW12 is abnormal (=140 mg/dL) and has increased by at least 50% of the reduction observed between Baseline and Visit OL22. • For patients in the DM/IGT subgroup with response at OL22, the proportion of patients with a loss of response with respect to hyperglycemic control from Visit OL22 to RW12, as compared between relacorilant and placebo arms, where loss of response is defined as follows: – Use of | — |
Countries
Austria, Bulgaria, Canada, Germany, Israel, Italy, Netherlands, Poland, Romania, Spain, United States
Contacts
Public ContactClinical Operations
Corcept Therapeutics Incorporated
Outcome results
None listed