A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome
SEISMIC
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
1 other identifier
interventional
50
1 country
17
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2007
CompletedFirst Submitted
Initial submission to the registry
December 5, 2007
CompletedFirst Posted
Study publicly available on registry
December 7, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2011
CompletedResults Posted
Study results publicly available
May 28, 2012
CompletedAugust 22, 2013
August 1, 2013
3.1 years
December 5, 2007
April 4, 2012
August 12, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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
Study Arms (1)
1
EXPERIMENTALInterventions
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.
Eligibility Criteria
You may qualify if:
- 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
- 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).
- Ectopic ACTH
- Ectopic CRF secretion
- Adrenal adenoma
- Adrenal carcinoma
- Adrenal autonomy
- Require medical treatment of hypercortisolemia
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, 35294, United States
AMCR Institute Inc.
Escondido, California, 92026, United States
Stanford University Medical Center
Stanford, California, 94305-5826, United States
The Center for Diabetes and Endocrine Care
Hollywood, Florida, 33021, United States
Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine
Chicago, Illinois, 60611, United States
The University of Chicago
Chicago, Illinois, 60637, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
University of New Mexico HSC
Albuquerque, New Mexico, 87131, United States
Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism
Cleveland, Ohio, 44195, United States
Oklahoma University Health Science Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health Sciences University
Portland, Oregon, 97239, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Diabetes and Glandular Disease Clinic
San Antonio, Texas, 78229, United States
Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin
Menomonee Falls, Wisconsin, 53051, United States
Related Publications (11)
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.
PMID: 8734015BACKGROUNDJohanssen 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.
PMID: 17984235BACKGROUNDMorris 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.
PMID: 12381547BACKGROUNDChu 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.
PMID: 11502780BACKGROUNDAgarwai MK. The antiglucocorticoid action of mifepristone. Pharmacol Ther. 1996;70(3):183-213. doi: 10.1016/0163-7258(96)00016-2.
PMID: 8888066BACKGROUNDMiller 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.
PMID: 7693447BACKGROUNDNieman 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.
PMID: 2991327BACKGROUNDFleseriu 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.
PMID: 22466348RESULTFein 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.
PMID: 26507877DERIVEDFleseriu 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.
PMID: 25013998DERIVEDWallia 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.
PMID: 23970725DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Corcept Therapeutics
Study Officials
- STUDY DIRECTOR
Coleman Gross
Corcept Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2007
First Posted
December 7, 2007
Study Start
December 1, 2007
Primary Completion
January 1, 2011
Last Updated
August 22, 2013
Results First Posted
May 28, 2012
Record last verified: 2013-08