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A Study of the Efficacy and Safety of CORLUX in the Treatment of Endogenous Cushing's Syndrome (SEISMIC)
This study is currently recruiting participants.
Verified by Corcept Therapeutics, November 2009
First Received: December 5, 2007   Last Updated: November 6, 2009   History of Changes
Sponsor: Corcept Therapeutics
Information provided by: Corcept Therapeutics
ClinicalTrials.gov Identifier: NCT00569582
  Purpose

Patients will receive Corlux (mifepristone) daily for up to 24 weeks. Assessments of the signs and symptoms of Cushing's syndrome will be obtained.


Condition Intervention Phase
Cushing's Syndrome
Drug: mifepristone
Phase III

Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official 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

Resource links provided by NLM:


Further study details as provided by Corcept Therapeutics:

Primary Outcome Measures:
  • Improvement in diabetes and/or glucose intolerance and/or hypertension and; drug safety. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Improvement in other symptoms of Cushing's Syndrome. [ Time Frame: 30 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2007
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00569582

Contacts
Contact: Chris Ward, Sponsor Contact 650-688-8807 cward@corcept.com

Locations
United States, Alabama
University of Alabama at Birmingham School of Medicine Recruiting
Birmingham, Alabama, United States, 35294
Contact: Marianne M Vetrano, RN     205-934-4112     mvetrano@uab.edu    
Principal Investigator: T. Brooks Vaughan, III, MD            
United States, California
AMCR Institute Inc. Recruiting
Escondido, California, United States, 92026
Contact: Laura Bedolla, CCRC     760-466-1523     lbedolla@amcrinstitute.com    
Principal Investigator: Timothy S Bailey, MD            
University of California San Francisco Withdrawn
San Francisco, California, United States, 94143
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305-5826
Contact: Kathleen Biederman, RN     650-721-6188     ktbieder@stanford.edu    
Principal Investigator: Laurence Katznelson, MD            
United States, Colorado
University of Colorado Health Science Center at Fitzsimon Recruiting
Aurora, Colorado, United States, 80045
Contact: Jennifer Tryggestad, MSSW     720-848-2692     jennifer.tryggestad@ucdenver.edu    
Principal Investigator: Janice Kerr, MD            
United States, Florida
The Center for Diabetes and Endocrine Care Recruiting
Hollywood, Florida, United States, 33021
Contact: Carrie-Ann Silva     954-963-7191 ext 243     casilvia@bellsouth.net    
Principal Investigator: Sam Lerman, MD            
United States, Illinois
Northwestern University Feinberg Medical; Division of Endocrinology, Metabolism & Molecular Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Daphne Adelman, RN, MBA     312-908-9002     d-adelman@northwestern.edu    
Principal Investigator: Mark Molitch, MD            
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Catherine DeSandre     773-834-0577     cdesandr@medicine.bsd.uchicago.edu    
Principal Investigator: Roy E Weiss, MD            
United States, Maryland
Sinai Hospital of Baltimore Recruiting
Baltimore, Maryland, United States, 21215
Contact: Alan Orpia, BSN, RN     410-601-0960     Aorpia@lifebridgehealth.org    
Principal Investigator: Henry G Fein, MD            
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Karen Pulaski-Liebert, BSN, RN     617-726-7473     kliebert@partners.org    
Principal Investigator: Beverly Biller, MD            
United States, Michigan
University of Michigan Medical Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Virginia E Uhley, PhD, RD     734-232-3618     vuhley@med.umich.edu    
Principal Investigator: David Schteingart, MD            
United States, Mississippi
University of Mississippi Medical Center Recruiting
Jackson, Mississippi, United States, 39216
Contact: Sheila Belk     601-815-5374     sbelk@medicine.umsmed.edu    
Principal Investigator: Christian A Koch, MD            
United States, New Mexico
University of New Mexico HSC Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Sofia Ramirez     505-275-7667     SoRamirez@salud.unm.edu    
Principal Investigator: Kathleen Colleran, MD            
United States, Ohio
Cleveland Clinic Foundation; Dept of Endocrinology, Diabetes & Metabolism Recruiting
Cleveland, Ohio, United States, 44195
Contact: Jackie Payne, RN     216-444-3694     paynej3@ccf.org    
Sub-Investigator: Amir Hekmat Hamrahian, MD            
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Katie Schweinsberg, RN     614-688-5881     kathleen.schweinsberg@osumc.edu    
Principal Investigator: Lawrence Steven Kirschner, MD, PhD            
United States, Oklahoma
Oklahoma University Health Science Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Sharon Buckley, RN, CDE     405-271-2814     sharon-buckley@ouhsc.edu    
Principal Investigator: Timothy Lyons, MD            
United States, Oregon
Oregon Health Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Chris Yedinak, MN, CFNP     503-494-6576     yedinakc@ohsu.edu    
Principal Investigator: Maria G Fleseriu, MD            
United States, Texas
Diabetes and Glandular Disease Clinic Recruiting
San Antonio, Texas, United States, 78229
Contact: Cheryl Sheets, RN, CCRC     210-615-5569     cheryl.sheets@cetero.com    
Principal Investigator: Mark Kipnes, MD            
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Amit Gode     214-648-0417     Amit.Gode@utsouthwestern.edu    
Principal Investigator: Michael J McPhaul, MD            
United States, Wisconsin
Endocrinology Center at North Hills, Froedtert and Medical College of Wisconsin Recruiting
Menomonee Falls, Wisconsin, United States, 53051
Contact: Gerard Coly, MD     414-456-7467     gcoly@mcw.edu    
Principal Investigator: Maria Grama Findling, MD            
Sponsors and Collaborators
Corcept Therapeutics
Investigators
Study Director: Coleman Gross Corcept Therapeutics
  More Information

Additional Information:
Publications:
Responsible Party: Corcept Therapeutics ( Coleman Gross )
Study ID Numbers: C-1073-400
Study First Received: December 5, 2007
Last Updated: November 6, 2009
ClinicalTrials.gov Identifier: NCT00569582     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Corcept Therapeutics:
Pituitary
Cushing's Disease
Cushing's Syndrome
Cushings
ACTH
Adrenocorticotropic hormone
Ectopic
Adrenal adenoma
Adrenal carcinoma
Adrenal autonomy
Cortisol
Hypercortisolemia
Cushinoid
Moon facies
Dorsalcervical fat
Plethora
Hirsutism
Violaceous striae
Hormone
Contraceptive
Endocrine
Cushing Syndrome
Cushing's Disease
Cortisol
Ectopic ACTH Secretion

Additional relevant MeSH terms:
Contraceptives, Postcoital, Synthetic
Contraceptive Agents
Hormone Antagonists
Physiological Effects of Drugs
Contraceptives, Oral
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptive Agents, Female
Adrenal Gland Diseases
Reproductive Control Agents
Hormones
Adrenocortical Hyperfunction
Adrenocorticotropic Hormone
Pathologic Processes
Syndrome
Therapeutic Uses
Abortifacient Agents
Menstruation-Inducing Agents
Contraceptives, Oral, Synthetic
Abortifacient Agents, Steroidal
Disease
Cushing Syndrome
Endocrine System Diseases
Mifepristone
Contraceptives, Postcoital
Luteolytic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 20, 2009