A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome
Condition: Cushing's Syndrome
MeSH terms: Cushing Syndrome; Syndrome
Intervention: mifepristone
Intervention description: 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.
Intervention MeSH terms: Mifepristone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

Summary:

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

Eligibility criteria:

        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

               1. 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).

               2. Ectopic ACTH

               3. Ectopic CRF secretion

               4. Adrenal adenoma

               5. Adrenal carcinoma

               6. 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.