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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00569582
Other study ID # C-1073-400
Secondary ID
Status Completed
Phase Phase 3
First received December 5, 2007
Last updated August 12, 2013
Start date December 2007

Study information

Verified date August 2013
Source Corcept Therapeutics
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 50
Est. completion date
Est. primary completion date January 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
mifepristone
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.

Locations

Country Name City State
United States University of New Mexico HSC Albuquerque New Mexico
United States University of Michigan Medical Center Ann Arbor Michigan
United States Sinai Hospital of Baltimore Baltimore Maryland
United States University of Alabama at Birmingham School of Medicine Birmingham Alabama
United States Massachusetts General Hospital Boston Massachusetts
United States Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine Chicago Illinois
United States The University of Chicago Chicago Illinois
United States Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism Cleveland Ohio
United States University of Texas Southwestern Medical Center Dallas Texas
United States AMCR Institute Inc. Escondido California
United States The Center for Diabetes and Endocrine Care Hollywood Florida
United States University of Mississippi Medical Center Jackson Mississippi
United States Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin Menomonee Falls Wisconsin
United States Oklahoma University Health Science Center Oklahoma City Oklahoma
United States Oregon Health Sciences University Portland Oregon
United States Diabetes and Glandular Disease Clinic San Antonio Texas
United States Stanford University Medical Center Stanford California

Sponsors (1)

Lead Sponsor Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (8)

Agarwai MK. The antiglucocorticoid action of mifepristone. Pharmacol Ther. 1996;70(3):183-213. Review. — View Citation

Chu JW, Matthias DF, Belanoff J, Schatzberg A, Hoffman AR, Feldman D. Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). J Clin Endocrinol Metab. 2001 Aug;86(8):3568-73. — View Citation

Fleseriu M, Biller BM, Findling JW, Molitch ME, Schteingart DE, Gross C; SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab — View Citation

Johanssen S, Allolio B. Mifepristone (RU 486) in Cushing's syndrome. Eur J Endocrinol. 2007 Nov;157(5):561-9. Review. — View Citation

Miller JW, Crapo L. The medical treatment of Cushing's syndrome. Endocr Rev. 1993 Aug;14(4):443-58. Review. — View Citation

Morris D, Grossman A. The medical management of Cushing's syndrome. Ann N Y Acad Sci. 2002 Sep;970:119-33. Review. — View Citation

Nieman LK, Chrousos GP, Kellner C, Spitz IM, Nisula BC, Cutler GB, Merriam GR, Bardin CW, Loriaux DL. Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. J Clin Endocrinol Metab. 1985 Sep;61(3):536-40. — View Citation

Sartor O, Cutler GB Jr. Mifepristone: treatment of Cushing's syndrome. Clin Obstet Gynecol. 1996 Jun;39(2):506-10. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Primary 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 No
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