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

NCT ID: NCT00569582

Last Updated: 2013-08-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

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.

Conditions

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Cushing's Syndrome

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Group Type EXPERIMENTAL

mifepristone

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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CORLUX

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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Corcept Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Coleman Gross

Role: STUDY_DIRECTOR

Corcept Therapeutics

Locations

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University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, United States

Site Status

AMCR Institute Inc.

Escondido, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

The Center for Diabetes and Endocrine Care

Hollywood, Florida, United States

Site Status

Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine

Chicago, Illinois, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of New Mexico HSC

Albuquerque, New Mexico, United States

Site Status

Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism

Cleveland, Ohio, United States

Site Status

Oklahoma University Health Science Center

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Diabetes and Glandular Disease Clinic

San Antonio, Texas, United States

Site Status

Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin

Menomonee Falls, Wisconsin, United States

Site Status

Countries

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United States

References

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Sartor O, Cutler GB Jr. Mifepristone: treatment of Cushing's syndrome. Clin Obstet Gynecol. 1996 Jun;39(2):506-10. doi: 10.1097/00003081-199606000-00024.

Reference Type BACKGROUND
PMID: 8734015 (View on PubMed)

Johanssen S, Allolio B. Mifepristone (RU 486) in Cushing's syndrome. Eur J Endocrinol. 2007 Nov;157(5):561-9. doi: 10.1530/EJE-07-0458.

Reference Type BACKGROUND
PMID: 17984235 (View on PubMed)

Morris D, Grossman A. The medical management of Cushing's syndrome. Ann N Y Acad Sci. 2002 Sep;970:119-33. doi: 10.1111/j.1749-6632.2002.tb04418.x.

Reference Type BACKGROUND
PMID: 12381547 (View on PubMed)

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. doi: 10.1210/jcem.86.8.7740.

Reference Type BACKGROUND
PMID: 11502780 (View on PubMed)

Agarwai MK. The antiglucocorticoid action of mifepristone. Pharmacol Ther. 1996;70(3):183-213. doi: 10.1016/0163-7258(96)00016-2.

Reference Type BACKGROUND
PMID: 8888066 (View on PubMed)

Miller JW, Crapo L. The medical treatment of Cushing's syndrome. Endocr Rev. 1993 Aug;14(4):443-58. doi: 10.1210/edrv-14-4-443. No abstract available.

Reference Type BACKGROUND
PMID: 7693447 (View on PubMed)

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. doi: 10.1210/jcem-61-3-536.

Reference Type BACKGROUND
PMID: 2991327 (View on PubMed)

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. 2012 Jun;97(6):2039-49. doi: 10.1210/jc.2011-3350. Epub 2012 Mar 30.

Reference Type RESULT
PMID: 22466348 (View on PubMed)

Fein HG, Vaughan TB 3rd, Kushner H, Cram D, Nguyen D. Sustained weight loss in patients treated with mifepristone for Cushing's syndrome: a follow-up analysis of the SEISMIC study and long-term extension. BMC Endocr Disord. 2015 Oct 27;15:63. doi: 10.1186/s12902-015-0059-5.

Reference Type DERIVED
PMID: 26507877 (View on PubMed)

Fleseriu M, Findling JW, Koch CA, Schlaffer SM, Buchfelder M, Gross C. Changes in plasma ACTH levels and corticotroph tumor size in patients with Cushing's disease during long-term treatment with the glucocorticoid receptor antagonist mifepristone. J Clin Endocrinol Metab. 2014 Oct;99(10):3718-27. doi: 10.1210/jc.2014-1843. Epub 2014 Jul 11.

Reference Type DERIVED
PMID: 25013998 (View on PubMed)

Wallia A, Colleran K, Purnell JQ, Gross C, Molitch ME. Improvement in insulin sensitivity during mifepristone treatment of Cushing syndrome: early and late effects. Diabetes Care. 2013 Sep;36(9):e147-8. doi: 10.2337/dc13-0246. No abstract available.

Reference Type DERIVED
PMID: 23970725 (View on PubMed)

Related Links

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http://www.corcept.com

Corporate Website

Other Identifiers

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C-1073-400

Identifier Type: -

Identifier Source: org_study_id