A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome

Study Overview
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Brief Summary
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Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.

Detailed Description
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Cushing's syndrome is a relatively rare disorder caused by prolonged exposure to high levels of the glucocorticoid hormone cortisol. Cushing's syndrome may result from elevated endogenous or exogenous sources of cortisol. Endogenous Cushing's syndrome resulting from cortisol overproduction by the adrenal glands is the subject of this protocol. Patients with exogenous Cushing's syndrome, which develops as a side effect of chronic administration of high doses of glucocorticoids, are not eligible for enrollment in this study. This will evaluate the safety and efficacy of mifepristone for treatment of the signs and symptoms of hypercortisolemia in patients with endogenous Cushing's syndrome from ACTH-dependent or adrenal disorders. The study will enroll subjects for whom the investigator has determined that medical treatment of endogenous hypercortisolemia is needed. Medical treatment may be intended to treat the effects of persistent or recurrent hypercortisolemia after surgery and/or radiation for Cushing's syndrome, to bridge the period of time for radiation to become effective, or when surgery is not feasible.

Official Title
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An Open-label Study of the Efficacy and Safety of CORLUX (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome

Conditions
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Cushing's Syndrome

Intervention / Treatment
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* Drug: mifepristone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals eligible for enrollment into this study are adult male and non-pregnant female adult patients who: Are at least 18 years of age Have a confirmed diagnosis of endogenous hypercortisolemia caused by ACTH dependent or ACTH independent etiologies, including Cushing's Disease (that has recurred after primary pituitary surgery, or has failed pituitary surgery, or has been treated with radiation therapy to the pituitary, or is not treatable with surgery, or exists in patients who are not candidates for surgery, and is confirmed by documentation of ACTH immuno-reactivity on a pathological evaluation of pituitary tissue from a previous surgical specimen or IPSS with a central-to-peripheral gradient (ratio) of >2 before or >3 after CRH administration). Ectopic ACTH Ectopic CRF secretion Adrenal adenoma Adrenal carcinoma Adrenal autonomy Require medical treatment of hypercortisolemia Have diabetes mellitus type 2 or glucose intolerance AND/OR have hypertension *Note: To be eligible for inclusion subjects must have documented evidence of persistent endogenous hypercortisolemia Exclusion Criteria: Individuals not eligible to be enrolled into the study are those who: Have de novo Cushing's disease and are surgical candidates for pituitary surgery. Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment. Taking medications within 14 days of the baseline visit (Day 1) that a) have a large first pass metabolism largely mediated by CYP3A4 and a narrow therapeutic margin and/or b) are strong CYP3A4 inhibitors. Female patients of reproductive potential, who are pregnant or who are unable or unwilling to use medically acceptable, non-hormonal methods of contraception during the study. Have received investigational treatment (drug, biological agent or device) within 30 days of Screening Have a history of an allergic reaction or intolerance to CORLUX (mifepristone) Have a non-endogenous source of hypercortisolemia such as factious hypercortisolemia (exogenous source of glucocorticoid, iatrogenic Cushing's syndrome), factious or therapeutic use of ACTH Have Pseudo-Cushing's syndrome. Receive PPARgamma agonist drugs (e.g. pioglitazone, rosiglitazone) within 4 months of Baseline (Day 1). Postmenopausal women with an intact uterus who have experienced unexplained vaginal bleeding within 12 months of Screening are excluded. Have renal failure as defined by a serum creatinine of ≥2.2 mg/dL.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: mifepristone<br>* Patients take mifepristone by mouth once a day. The dose is increased during scheduled timepoints during the study or until symptoms improve or the highest dosage allowed is reached. Dose escalation will be based upon weight. During clinic visits, blood pressure, glucose tolerance and blood chemistries are measured and EKG and urinalysis will be performed.<br>* Other names: CORLUX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in Diabetes and/or Glucose Intolerance. | Responder is defined as subject with a decrease greater than or equal to 25% in area under the curve for glucose on 2-hour oral glucose test from baseline to week 24 or last visit, for Cushing's patients with type-2 diabetes mellitus/impaired glucose tolerance. | Baseline to Week 24 | 
| Decrease in Diastolic Blood Pressure. | Responder is defined as subject with a decrease greater than or equal to 5mm Hg in diastolic blood pressure from baseline to week 24 or last visit. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cushing's Disease, Cushing's Syndrome, Cushings, Pituitary, ACTH, Adrenocorticotropic hormone, Ectopic, Adrenal adenoma, Adrenal carcinoma, Adrenal autonomy, Cortisol, Hypercortisolemia, Cushingoid, Moon facies, Dorsocervical fat, Plethora, Hirsutism, Violaceous striae, Hormone, Contraceptive, Endocrine, Cushing Syndrome, Ectopic ACTH Secretion