Clinical trial: A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome (NCT00569582)

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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the office due to weight gain and fatigue.  He is not able to lift heavy objects or climb stairs. Family history is positive for DM type 2 and HTN in his father.  Blood pressure is 165/90 mm Hg and pulse is 85/min.  On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities.  Fasting plasma glucose level is 138 mg/dL and 24-hour urinary cortisol is twice the upper normal limit.  Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels.  Serum ACTH levels are high-normal. This patient's findings are consistent with endogenous Cushing Syndrome.

Patient description (patient's own words): I'm a 47-year-old man. I went to the clinic because I had been gaining weight and had increased fatigue over the past few weeks. I was not able to lift heavy objects or even climb the stairs. My dad was diagnosed with type 2 diabetes and high blood pressure. During the exam, they took my blood pressure, which was 165/90 mm Hg, and my pulse was 85/min. They found out that I have weaknesses in both of my arms and legs. I also did a blood test on an empty stomach, and I had a glucose level of 138 mg/dL, and twice the upper normal limit of cortisol. I had high-normal levels of ACTH. The doctor said I suffer from endogenous Cushing Syndrome.

Does the patient match the trial criteria? Contradiction