E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Endogenous Cushing Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Cushing Syndrome caused by the body producing more cortisol than it needs |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011657 |
E.1.2 | Term | Cushings syndrome |
E.1.2 | System Organ Class | 100000004860 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the long-term safety of relacorilant in the treatment of the signs and symptoms of endogenous Cushing syndrome |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term benefit of relacorilant in the treatment of signs and symptoms of endogenous Cushing syndrome |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Patients 1. Have completed a Corcept-sponsored study of relacorilant in endogenous Cushing syndrome through the treatment period with at least 80% adherence with scheduled dosing and visits. 2. According to Investigator’s opinion will benefit from continuing treatment with relacorilant. 3. Provide written informed consent. 4. If a female of childbearing potential, patients must be willing to use a highly effective method of contraception from 30 days before study entry until 30 days after the last dose of study drug. Male patients with a female partner must agree to 2 forms of contraception, one of which must be a double-barrier method, from study entry until 30 days after the last dose of study drug. Highly effective methods of contraception include abstinence, oral contraceptives combined with a barrier method, diaphragm with vaginal spermicide, intrauterine device, male condom and partner using vaginal spermicide, and surgical sterilization (≥6 months postsurgery). 5. Are willing to continue to refrain from using drugs that inhibit steroid biosynthesis by the adrenal cortex or ACTH secretion by a pituitary or extrapituitary ACTH secreting tumor. Mitotane is acceptable in patients with adrenal carcinoma. 6. Are able to return to the investigative site to complete the study evaluations outlined in the protocol. 7. For patients with Cushing syndrome due to an ACTH-secreting pituitary tumor, are able to obtain pituitary MRI imaging (obtained up to 3 months before to 6 weeks after start of treatment in this study) to assess changes in tumor size during dosing.
Patients Who Enter Study >8 Weeks After Completing the Parent Study 8. Have a diagnosis of endogenous Cushing syndrome confirmed by 2 of the 3 following biochemical test criteria: • Urinary free cortisol above the upper limit of normal (ULN) (50.0 μg/24 h) in at least 2 complete 24-hour collections within 3 weeks before Day 1. • Late-night salivary cortisol above the ULN in at least 2 collections using a salivette within 3 weeks before Day 1. • Results from the dexamethasone suppression test performed during the parent study. Patients requiring washout of a medication for Cushing syndrome must complete the screening 24-hour UFC tests and salivary cortisol tests after a minimum washout of 2 weeks for adrenostatic medications and short-acting somatostatin analogs, 4 weeks for mifepristone and dopamine agonists, and 6 weeks for long-acting somatostatin ligands and within 3 weeks before Day 1 dosing.
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E.4 | Principal exclusion criteria |
1. Have been prematurely discontinued from relacorilant study treatment in the parent study for any reason 2. Are planning to start another Cushing syndrome drug after starting participation in this extension study. 3. Have an acute or unstable medical problem that could be aggravated by relacorilant treatment. 4. Are taking the following medications from the times specified below before the Study CORT125134-452 Day 1 visit and/or through the entire study period: • Medications used in the treatment of Cushing syndrome, with the exception of relacorilant, are prohibited: – Adrenostatic medications: metyrapone, ketoconazole, fluconazole, aminoglutethimide, or etomidate 2 weeks before Day 1 through the end of this study – Neuromodulator drugs that act at the hypothalamic-pituitary level: serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), gamma-aminobutyric acid agonists (sodium valproate), and somatostatin receptor ligands (octreotide long-acting release [LAR], pasireotide LAR, lanreotide) from 8 weeks before Day 1 through the end of this study. Use of short-acting somatostatin analogs (octreotide, pasireotide) from 4 weeks before Day 1 through the end of this study. • Mifepristone, from 4 weeks before Day 1 through the end of this study. • Strong CYP3A4 inhibitors (including grapefruit, grapefruit juice, or grapefruit-containing products) during treatment with relacorilant. 5. Plan to use systemic, potent (Group III), and potent intra-articular corticosteroids from Day 1 through the end of the study. 6. Have received investigational treatment (drug, biological agent, or device) other than relacorilant within 4 weeks of study entry. 7. Have a history of an allergic reaction or intolerance to relacorilant. 8. Have uncorrected hypokalemia (potassium level of < 3.5 mEq/L) within 2 weeks before enrollment in this study (Day 1). 9. Have uncontrolled, clinically significant hypothyroidism or hyperthyroidism. 10. Have renal failure as defined by a serum creatinine of ≥2.2 mg/dL. 11. Have elevated total bilirubin >1.5 × the ULN or elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × ULN. 12. Have a clinically significant ECG abnormality at baseline, which, in the opinion of the Investigator, will make the patient an unsuitable candidate for the study. 13. Have a confirmed baseline QT interval corrected using Fridericia’s formula (QTcF) >450 ms for males and >470 ms for females in the presence of a normal QRS interval (QRS <120 ms) or a history of additional risk factors for torsades de pointes. 14. Women of childbearing potential: are pregnant based on serum pregnancy test. 15. Have an ongoing SAE that started in the parent study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of TEAEs • Changes from baseline levels in clinical laboratory measurements • Changes from baseline in physical examinations and vital sign measurements • Changes from baseline in ECG variables • Changes from baseline in pituitary tumors based on MRI scans in patients with Cushing disease. • PK measurements |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly : - Incidence of TEAEs
Every 3 and 12 Months and at End of Study: - Adverse event monitoring - Clinical laboratory measurements - Physical examination - Vital signs including BP, heart rate, respiratory rate, and oral body temperature - 12-Lead ECG - PK sampling
Every 12 Months and at End of Study: - Pituitary MRI scan
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E.5.2 | Secondary end point(s) |
Changes from baseline in the following: - HbA1c and insulin resistance indices in patients with Diabetes mellitus or glucose intolerance if an oral glucose tolerance test (OGTT) was a key efficacy assessment in the parent study – BP by ambulatory BP measurements (ABPM) in patients with uncontrolled hypertension (HTN) if this was a key efficacy assessment in the parent study and in patients with controlled HTN taking at least one anti-HTN medication – Physician’s Global Assessment of Disease Severity – Weight and waist circumference – Quality-of-life (CushingQoL) questionnaire – Biochemical markers of bone remodeling – HPA axis markers – Cortisol concentration in blood, urine, and saliva – Lipid levels – Sex steroid hormone and gonadotropin levels – Menstrual cycle characterization (premenopausal women not taking hormonal contraceptive medication) – Thyroid function tests |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 3 and 12 Months and at End of Study: - HbA1c - ABPM - Physician’s Global Assessment - Weight and waist circumference - CushingQoL Questionnaire - Biochemical markers of bone remodeling - HPA axis parameters - Late-night salivary cortisol - Lipid panel (fasting) - Sex hormone levels - Menstrual cycle information
- Thyroid function tests |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Hungary |
Italy |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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In accordance with European Union and FDA regulations, the end of study is defined as the date of last contact (visit, telephone, e-mail) with any study patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 18 |