Endogenous Cushing’s Syndrome MedDRA version: 20.0 Level: LLT Classification code 10011657 Term: Cushings syndrome System Organ Class: 100000004860
Conditions
Interventions
Product Code: CORT125134
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Relacorilant
CAS Number: 1496510-51-0
Current Sponsor c
Sponsors
Corcept Therapeutics Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is a male or female adult, 18–80 years of age 2. Has a diagnosis of endogenous Cushing's syndrome confirmed by: At least two of the following test criteria (Nieman 2008): •Urinary free cortisol above the upper limit of normal (ULN) (50.0 µg/24h) in at least 2, and up to 4, complete 24 hour collections within 3 weeks prior to Day 1 (baseline) •Late-night salivary cortisol above the ULN (at least 2, and up to 4, collections using a salivette) within 3 weeks prior to Day 1 (baseline) •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 the ICF is signed. And At least two of the following clinical signs and symptoms of Cushing’s syndrome: •Facial characteristics of a Cushingoid appearance (moon facies, dorsocervical fat pad, plethora) •Increased body weight or central obesity •Proximal muscle weakness •Low bone mass (dual energy X-ray absorptiometry [DXA] T 5 µg/dL serum cortisol) on either 1-mg overnight or 2-mg 48-hour dexamethasone suppression testing during screening • Low or suppressed ACTH (126 mg/dL and a 2-hour oral glucose tolerance test [oGTT] result for plasma glucose =200 mg/dL at 2 hours (Standards of Medical Care in Diabetes – 2015) •Has impaired glucose tolerance (2-hour oGTT result for plasma glucose in the range of =140 mg/dL to <200 mg/dL) (Standards of Medical Care in Diabetes – 2015) • Has hypertension (mean systolic BP of 130–170 mmHg and/or a mean diastolic BP of 85–110 mmHg) based o
Exclusion criteria
Exclusion criteria: 1. Has a non-endogenous source of hypercortisolemia 2. Has pseudo-Cushing’s syndrome. Patients with known or suspected pseudo-Cushing’s 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 (Yanovski 1993, Giraldi 2007, Yanovski 1998) to rule-in or rule-out this possibility. 3. Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism 4. Has poorly controlled hypertension, defined as systolic BP >170 mmHg or diastolic BP >110 mmHg at screening 5. Has Stage 4 renal failure (ie, glomerular filtration rate =29 mL/min) 6. Has elevated total bilirubin >1.5×ULN or elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×ULN 7. For patients with diabetes or abnormal oGTT at screening: Has glycated hemoglobin (HbA1c) of >12% within 3 months of first dose of study drug 8. Has a screening hemoglobin level of 450 ms for males and >470 ms for females (using Fridericia’s correction) in the presence of a normal QRS interval (QRS <120 ms) or a history of additional risk factors for torsades de pointes 11. Is currently receiving chemotherapy for a tumor related to Cushing’s syndrome 12. Had radiation therapy for Cushing’s syndrome-related tumor within 1 year of screening period 13. Is planning surgery or radiation therapy for Cushing’s syndrome-related tumor during the study 14. Has used or plans to use any of the following treatments for Cushing’s syndrome, as specified: •Adrenostatic medications: metyrapone, ketoconazole, fluconazole, aminoglutethimide, or etomidate from 4 weeks prior to baseline (Day 1) through the follow-up visit •Adrenolytic medications: oIn Group 1, any patients taking mitotane oIn Group 2 only, patients with adrenocortical carcinomas taking mitotane whose dose has not been stable for at least 2 months prior to baseline (Day 1) or in whom increases in the mitotane dosage are expected through the end of dosing •Neuromodulator drugs that act at the hypothalamic-pituitary level: serotonin antagonists (cyproheptadine, ketanserin, retanserin), 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 baseline (Day 1) through the follow-up visit. Use of short-acting somatostatin analogs (octreotide, pasireotide) from 4 weeks prior to baseline (Day 1) through the follow-up visit. •Mifepristone, from 6 weeks before baseline (Day 1) through the follow-up visit 15. Has started or increased (or plans to start or increase) the dose of an antidepressant medication (eg, selective serotonin reuptake inhibitors or tricyclic compound) from 6 weeks before baseline (Day 1) through the end of the study dosing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and efficacy of CORT125134 in patients with endogenous Cushing’s syndrome. ;Secondary Objective: To assess the evidence of reduction in cortisol activity following treatment with CORT125134 in patients with endogenous Cushing’s syndrome based on improvement in blood glucose control and/or blood pressure (BP).; Primary end point(s): Key Efficacy: •Oral glucose tolerance test (oGTT) (impaired glucose tolerance/diabetes subgroup only) •Ambulatory BP measurement (hypertension subgroup only) Pharmacokinetics: •Blood levels of CORT125134 and metabolites Safety: •Physical examination findings, vital signs, ECG results, pregnancy tests, clinical laboratory test results (hematology and chemistry panels), adverse events (AEs), and concomitant medications ; Timepoint(s) of evaluation of this end point: •oGTT at baseline (Day 1) and Week 4, Week 8, and Week 12/early termination (ET) visits. •Ambulatory BP for all at screening. For hypertension subgroup baseline, weeks 2, 4, 6, 8, 10, and 12/ET •Pharmacokinetics will be measured predose and at 1, 2, 4, 6, and 8 hours postdose at Weeks 2, 6, and 10, and predose only at Weeks 4, 8, and 12/early termination •Safety assessments performed at baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10, and Week 12/ET visits and follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Exploratory efficacy assessments •Physician’s Global Assessment •HbA1c •Fructosamine •Adiponectin •24-hour urinary free cortisol (UFC) with creatinine •Late-night salivary cortisol •Body weight, waist circumference •Beck Depression Inventory (BDI-II), Trail Making Test, CushingQoL •Lipid panel •Sit-to-stand test •Sex hormone levels •Menstrual cycle characterization (premenopausal women not on hormonal birth control) •Coagulation tests •Glucocorticoid receptor (GR) biomarker tests •Bone markers (serum bone alkaline phosphatase, osteocalcin, urine N telopeptides of type 1 collagen [NTx], calcium from 24-hour UFC) •Hypothalamic-pituitary-adrenal (HPA) axis markers, including plasma ACTH and serum cortisol concentrations •ACTH precursors •High-sensitivity C-reactive protein concentrations •24-hour urine calcium and sodium •Insulin-like growth factor (IGF-1) •Thyroid function tests ;Timepoint(s) of evaluation of this end point: At baseline, Weeks 2, 4, 6, 8, 10, 12/ET, and follow-up | — |
Countries
Hungary, Netherlands, United Kingdom, United States
Contacts
Public ContactCORT451 Project Manager (11598)
Chiltern International Ltd
Outcome results
None listed