Cushing's Syndrome Clinical Trial
— SEISMICOfficial title:
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
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 |
Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.
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. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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 |
Lead Sponsor | Collaborator |
---|---|
Corcept Therapeutics |
United States,
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
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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